zotero.bib

@article{ostberg_analysis_2013,
	series = {Enzymology and {Molecular} {Biology} of {Carbonyl} {Metabolism} 16},
	title = {Analysis of mammalian alcohol dehydrogenase 5 ({ADH}5): {Characterisation} of rat {ADH}5 with comparisons to the corresponding human variant},
	volume = {202},
	issn = {0009-2797},
	shorttitle = {Analysis of mammalian alcohol dehydrogenase 5 ({ADH}5)},
	doi = {10.1016/j.cbi.2012.11.002},
	abstract = {Alcohol dehydrogenase 5 (ADH5) is a member of the mammalian alcohol dehydrogenase family of yet undefined functions. ADH5 was first identified at the DNA level in human and deer mouse. A rat alcohol dehydrogenase structure of similar type has been isolated at the cDNA level using human ADH5 as a screening probe, where the rat cDNA structure displayed several atypical properties. mRNA for rat ADH5 was found in multiple tissues, especially in the kidney. In vitro translation experiments indicated that rat ADH5 is expressed as efficiently as ADH1 and furthermore, rat ADH5 was readily expressed in COS cells fused to Green Fluorescent Protein. However, no soluble ADH5 protein could be heterologously expressed in Escherichia coli cells with expression systems successfully used for other mammalian ADHs, including fused to glutathione-S-transferase. Molecular modelling of the enzyme indicated that the protein does not fold in a productive way, which can be the explanation why no stable and active ADH5 has been isolated. These results indicate that ADH5, while readily expressed at the mRNA level, does not behave similarly to other mammalian ADHs investigated. The results, in vitro and in silico, suggest an unstable ADH5 structure, which can explain for why no active and stable protein can be isolated. Further possibilities are conceivable: the ADH5 protein may have to interact with a stabiliser, or the gene is actually a pseudogene.},
	number = {1–3},
	urldate = {2014-10-02},
	journal = {Chem. Biol. Interact.},
	author = {Östberg, Linus J. and Strömberg, Patrik and Hedberg, Jesper J. and Persson, Bengt and Höög, Jan-Olov},
	month = feb,
	year = {2013},
	keywords = {ADH classes, Alcohol Dehydrogenase, Enzyme family, Molecular modelling, Protein expression},
	pages = {97--103}
}

@misc{munroe_xkcd_2017,
	type = {Webcomic},
	title = {xkcd},
	copyright = {CC BY-NC 2.5},
	shorttitle = {xkcd},
	url = {https://xkcd.com/1605/},
	language = {English},
	urldate = {2017-03-22},
	journal = {xkcd: DNA},
	author = {Munroe, Randall},
	month = mar,
	year = {2017}
}

@article{altchul_basic_1990,
	title = {Basic {Local} {Alignment} {Search} {Tool}},
	volume = {215},
	journal = {J. Mol. Biol.},
	author = {Altchul, SF and Gish, W and Miller, W and Myers, EW and Lipman, DJ},
	year = {1990},
	pages = {403--410}
}

@article{thompson_balibase_2005,
	title = {{BAliBASE} 3.0: latest developments of the multiple sequence alignment benchmark},
	volume = {61},
	issn = {1097-0134},
	shorttitle = {{BAliBASE} 3.0},
	doi = {10.1002/prot.20527},
	abstract = {Multiple sequence alignment is one of the cornerstones of modern molecular biology. It is used to identify conserved motifs, to determine protein domains, in 2D/3D structure prediction by homology and in evolutionary studies. Recently, high-throughput technologies such as genome sequencing and structural proteomics have lead to an explosion in the amount of sequence and structure information available. In response, several new multiple alignment methods have been developed that improve both the efficiency and the quality of protein alignments. Consequently, the benchmarks used to evaluate and compare these methods must also evolve. We present here the latest release of the most widely used multiple alignment benchmark, BAliBASE, which provides high quality, manually refined, reference alignments based on 3D structural superpositions. Version 3.0 of BAliBASE includes new, more challenging test cases, representing the real problems encountered when aligning large sets of complex sequences. Using a novel, semiautomatic update protocol, the number of protein families in the benchmark has been increased and representative test cases are now available that cover most of the protein fold space. The total number of proteins in BAliBASE has also been significantly increased from 1444 to 6255 sequences. In addition, full-length sequences are now provided for all test cases, which represent difficult cases for both global and local alignment programs. Finally, the BAliBASE Web site (http://www-bio3d-igbmc.u-strasbg.fr/balibase) has been completely redesigned to provide a more user-friendly, interactive interface for the visualization of the BAliBASE reference alignments and the associated annotations.},
	language = {eng},
	number = {1},
	journal = {Proteins},
	author = {Thompson, Julie D. and Koehl, Patrice and Ripp, Raymond and Poch, Olivier},
	month = oct,
	year = {2005},
	pmid = {16044462},
	keywords = {Amino Acid Sequence, Benchmarking, Databases, Protein, Internet, Molecular Sequence Data, Protein Folding, Proteins, Protein Structure, Quaternary, Sequence Alignment, Software, Structural Homology, Protein},
	pages = {127--136}
}

@article{katoh_mafft_2013,
	title = {{MAFFT} multiple sequence alignment software version 7: improvements in performance and usability},
	volume = {30},
	issn = {1537-1719},
	shorttitle = {{MAFFT} multiple sequence alignment software version 7},
	doi = {10.1093/molbev/mst010},
	abstract = {We report a major update of the MAFFT multiple sequence alignment program. This version has several new features, including options for adding unaligned sequences into an existing alignment, adjustment of direction in nucleotide alignment, constrained alignment and parallel processing, which were implemented after the previous major update. This report shows actual examples to explain how these features work, alone and in combination. Some examples incorrectly aligned by MAFFT are also shown to clarify its limitations. We discuss how to avoid misalignments, and our ongoing efforts to overcome such limitations.},
	language = {eng},
	number = {4},
	journal = {Mol. Biol. Evol.},
	author = {Katoh, Kazutaka and Standley, Daron M.},
	month = apr,
	year = {2013},
	pmid = {23329690},
	pmcid = {PMC3603318},
	keywords = {Algorithms, Amino Acid Sequence, Base Sequence, DNA, Fungal, DNA, Ribosomal, DNA, Ribosomal Spacer, Fungi, Humans, Models, Genetic, Molecular Sequence Data, Phylogeny, Protein Structure, Tertiary, Quality Improvement, Ribonucleases, Ribosome Subunits, Small, Bacterial, RNA, Bacterial, Sequence Alignment, Software},
	pages = {772--780}
}

@article{jornvall_alcohol_2015,
	series = {17th {International} {Workshop} on the {Enzymology} and {Molecular} {Biology} of {Carbonyl} {Metabolism}},
	title = {Alcohol dehydrogenase, {SDR} and {MDR} structural stages, present update and altered era},
	volume = {234},
	issn = {0009-2797},
	doi = {10.1016/j.cbi.2014.10.017},
	abstract = {It is now about half a century since molecular research on alcohol dehydrogenase (ADH), short-chain dehydrogenase/reductase (SDR) and medium-chain dehydrogenase/reductase (MDR) started. During this time, at least four stages of research can be distinguished, which led to many ADH, SDR and MDR structures from which their origins could be traced. An introductory summary of these stages is given, followed by a current update on the now known structures, including the present pattern of mammalian MDR–ADH enzymes into six classes and their evolutionary relationships. In spite of the wide spread in evolutionary changes from the “constant” class III to the more “variable” other classes, the change in class V (only confirmed as a transcript in humans) and class VI (absent in humans) are also restricted. Such spread in variability is visible also in other dehydrogenases, but not always so restricted in other co-evolving proteins we have studied. Finally, the shift in era of present ADH research is highlighted, as well as levels of likely future continuation.},
	urldate = {2015-04-27},
	journal = {Chem. Biol. Interact.},
	author = {Jörnvall, Hans and Landreh, Michael and Östberg, Linus J.},
	month = jun,
	year = {2015},
	keywords = {Alcohol dehydrogenase (ADH), Enzymogenesis, Evolution, Gene duplication, Medium-chain dehydrogenase/reductase (MDR), Short-chain dehydrogenase/reductase (SDR)},
	pages = {75--79}
}

@article{sakurai_quantitative_2007,
	title = {Quantitative structure-activity relationship analysis and molecular dynamics simulation to functionally validate nonsynonymous polymorphisms of human {ABC} transporter {ABCB}1 ({P}-glycoprotein/{MDR}1)},
	volume = {46},
	journal = {Biochemistry},
	author = {Sakurai, A. and Onishi, Y. and Hirano, H. and Seigneuret, M. and Obanayama, K. and Kim, G. and Liew, E. L. and Sakaeda, T. and Yoshiura, K. and Niikawa, N. and Sakurai, M. and Ishikawa, T.},
	year = {2007},
	pages = {7678--7693}
}

@article{chen_enzymatic_1991,
	title = {Enzymatic properties of the protein encoded by newly cloned human alcohol dehydrogenase {ADH}6 gene},
	volume = {181},
	issn = {0006-291X},
	doi = {10.1016/0006-291X(91)91253-9},
	abstract = {Five non-allelic genes which encode five types of alcohol dehydrogenase subunits have been identified in humans. An additional gene (ADH6) and cDNA, whose coding sequences were not highly analogous to any of the known alcohol dehydrogenase subunits, were recently cloned (Yasunami et al., Proc. Natl. Acad. Sci. USA 88, 7610–7614, 1991). The full-length ADH6 cDNA was expressed in the E.coli expression system and in the invitro translation system of rabbit reticulocytes. The protein produced had its isoelectric point at pH 8.6, optimum pH at pH 10, and a lower Km for benzylalcohol than for ethanol and propanol. These characteristics are compatible to the properties of μ- or σ-alcohol dehydrogenase isozyme existing in human stomach, indicating that ADH6 gene encodes the μ- or σ-alcohol dehydrogenase subunit.},
	number = {2},
	urldate = {2013-08-26},
	journal = {Biochem. Biophys. Res. Commun.},
	author = {Chen, Cheng-Sheng and Yoshida, Akira},
	month = dec,
	year = {1991},
	pages = {743--747},
	file = {ScienceDirect Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/W64D95AV/Chen and Yoshida - 1991 - Enzymatic properties of the protein encoded by new.pdf:application/pdf;ScienceDirect Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/3ZJWMIPA/0006291X91912539.html:text/html}
}

@article{liu_rapid_2009,
	title = {Rapid and accurate large-scale coestimation of sequence alignments and phylogenetic trees},
	volume = {324},
	issn = {1095-9203},
	doi = {10.1126/science.1171243},
	abstract = {Inferring an accurate evolutionary tree of life requires high-quality alignments of molecular sequence data sets from large numbers of species. However, this task is often difficult, slow, and idiosyncratic, especially when the sequences are highly diverged or include high rates of insertions and deletions (collectively known as indels). We present SATé (simultaneous alignment and tree estimation), an automated method to quickly and accurately estimate both DNA alignments and trees with the maximum likelihood criterion. In our study, it improved tree and alignment accuracy compared to the best two-phase methods currently available for data sets of up to 1000 sequences, showing that coestimation can be both rapid and accurate in phylogenetic studies.},
	language = {eng},
	number = {5934},
	journal = {Science},
	author = {Liu, Kevin and Raghavan, Sindhu and Nelesen, Serita and Linder, C. Randal and Warnow, Tandy},
	month = jun,
	year = {2009},
	pmid = {19541996},
	keywords = {Algorithms, Automation, Computer Simulation, DNA, Evolution, Molecular, Likelihood Functions, Phylogeny, Sequence Alignment, Software},
	pages = {1561--1564}
}

@article{webb_comparative_2016,
	title = {Comparative {Protein} {Structure} {Modeling} {Using} {MODELLER}},
	volume = {54},
	issn = {1934-340X},
	doi = {10.1002/cpbi.3},
	abstract = {Comparative protein structure modeling predicts the three-dimensional structure of a given protein sequence (target) based primarily on its alignment to one or more proteins of known structure (templates). The prediction process consists of fold assignment, target-template alignment, model building, and model evaluation. This unit describes how to calculate comparative models using the program MODELLER and how to use the ModBase database of such models, and discusses all four steps of comparative modeling, frequently observed errors, and some applications. Modeling lactate dehydrogenase from Trichomonas vaginalis (TvLDH) is described as an example. The download and installation of the MODELLER software is also described. © 2016 by John Wiley \& Sons, Inc.},
	language = {eng},
	journal = {Curr Protoc Bioinformatics},
	author = {Webb, Benjamin and Sali, Andrej},
	month = jun,
	year = {2016},
	pmid = {27322406},
	pmcid = {PMC5031415},
	keywords = {comparative modeling, ModBase, MODELLER, protein fold, protein structure, structure prediction},
	pages = {5.6.1--5.6.37}
}

@article{estonius_alcohol_1996,
	title = {Alcohol dehydrogenase in human tissues: localisation of transcripts coding for five classes of the enzyme},
	volume = {397},
	issn = {0014-5793},
	shorttitle = {Alcohol dehydrogenase in human tissues},
	abstract = {Tissue distribution of the five identified classes of human alcohol dehydrogenase was studied by assessment of mRNA levels in 23 adult and four fetal tissues. Alcohol dehydrogenase of class I was found in most tissues, brain and placenta excluded, but expression levels among tissues differed widely. The distribution pattern of class III transcripts was consistent with those of housekeeping enzymes while, in contrast, class IV transcripts were found only in stomach. Transcripts of multiple length were detected for most classes and were due to different gene products arising through the use of different poly-A signals or transcription from different gene loci. Both class II and class V showed a pattern of liver-enriched expression. However, low mRNA levels were detected also in stomach, pancreas and small intestine for class II, and in fetal kidney and small intestine for class V. Significantly higher levels of class V transcripts were present in fetal liver when compared with levels in adult liver, which suggests that human class V is a predominantly fetal alcohol dehydrogenase.},
	language = {eng},
	number = {2-3},
	journal = {FEBS Lett.},
	author = {Estonius, M. and Svensson, S. and Höög, J-O},
	month = nov,
	year = {1996},
	pmid = {8955375},
	keywords = {Alcohol Dehydrogenase, Blotting, Northern, Brain, Cloning, Molecular, Digestive System, Female, Genitalia, Humans, Kidney, Liver, Lymphoid Tissue, Male, Organ Specificity, Placenta, RNA, Messenger, Tissue Distribution},
	pages = {338--342}
}

@article{altschul_gapped_1997,
	title = {Gapped {BLAST} and {PSI}-{BLAST}: a new generation of protein database search programs},
	volume = {25},
	issn = {0305-1048},
	shorttitle = {Gapped {BLAST} and {PSI}-{BLAST}},
	doi = {10.1093/nar/25.17.3389},
	number = {17},
	urldate = {2017-01-27},
	journal = {Nucl Acids Res},
	author = {Altschul, Stephen F. and Madden, Thomas L. and Schäffer, Alejandro A. and Zhang, Jinghui and Zhang, Zheng and Miller, Webb and Lipman, David J.},
	month = sep,
	year = {1997},
	pages = {3389--3402}
}

@article{sali_comparative_1993,
	title = {Comparative protein modelling by satisfaction of spatial restraints},
	volume = {234},
	issn = {0022-2836},
	doi = {10.1006/jmbi.1993.1626},
	abstract = {We describe a comparative protein modelling method designed to find the most probable structure for a sequence given its alignment with related structures. The three-dimensional (3D) model is obtained by optimally satisfying spatial restraints derived from the alignment and expressed as probability density functions (pdfs) for the features restrained. For example, the probabilities for main-chain conformations of a modelled residue may be restrained by its residue type, main-chain conformation of an equivalent residue in a related protein, and the local similarity between the two sequences. Several such pdfs are obtained from the correlations between structural features in 17 families of homologous proteins which have been aligned on the basis of their 3D structures. The pdfs restrain C alpha-C alpha distances, main-chain N-O distances, main-chain and side-chain dihedral angles. A smoothing procedure is used in the derivation of these relationships to minimize the problem of a sparse database. The 3D model of a protein is obtained by optimization of the molecular pdf such that the model violates the input restraints as little as possible. The molecular pdf is derived as a combination of pdfs restraining individual spatial features of the whole molecule. The optimization procedure is a variable target function method that applies the conjugate gradients algorithm to positions of all non-hydrogen atoms. The method is automated and is illustrated by the modelling of trypsin from two other serine proteinases.},
	language = {eng},
	number = {3},
	journal = {J. Mol. Biol.},
	author = {Sali, A. and Blundell, T. L.},
	month = dec,
	year = {1993},
	pmid = {8254673},
	keywords = {Amino Acid Sequence, Animals, Enzymes, Humans, Kallikreins, Mathematics, Models, Theoretical, Molecular Sequence Data, Pancreatic Elastase, Probability, Protein Conformation, Proteins, Sequence Homology, Amino Acid, Software, Thermodynamics, Tissue Kallikreins, Trypsin},
	pages = {779--815}
}

@article{jones_genthreader:_1999,
	title = {{GenTHREADER}: an efficient and reliable protein fold recognition method for genomic sequences},
	volume = {287},
	number = {4},
	journal = {J. Mol. Biol.},
	author = {Jones, DT},
	year = {1999},
	pages = {797--815}
}

@article{chenna_multiple_2003,
	title = {Multiple sequence alignment with the {Clustal} series of programs},
	volume = {31},
	journal = {Nucleic Acids Res.},
	author = {Chenna, R. and Sugawara, H. and Koike, T. and Lopez, R. and Gibson, T. J. and Higgins, D. G. and Thompson, J. D},
	year = {2003},
	pages = {3497--3500}
}

@article{hoog_mammalian_2011,
	title = {Mammalian alcohol dehydrogenases – {A} comparative investigation at gene and protein levels},
	volume = {191},
	issn = {0009-2797},
	shorttitle = {Enzymology and {Molecular} {Biology} of {Carbonyl} {Metabolism} 15th {International} {Meeting} on {Enzymology} and {Molecular} {Biology} of {Carbonyl} {Metabolism}},
	doi = {10.1016/j.cbi.2011.01.028},
	abstract = {Mammalian alcohol dehydrogenase (ADH) can be divided into six classes, ADH1–ADH6, according to primary structure and function, where the classes are further subdivided into isozymes and allelic forms. With the increasing amount of available genomic data a general pattern is possible to trace within the mammalian ADH gene and protein families. The transcriptional order for the ADH genes in all mammalian genomes is the same (ADH4–ADH1–ADH6–ADH5–ADH2–ADH3), but the cluster is found on different chromosomes in different species. However, in primates only ADH1–ADH5 are present, where the loss of ADH6 may have occurred simultaneously as the split into ADH1 isoforms. ADH3, also denoted glutathione-dependent formaldehyde dehydrogenase and S-nitrosoglutathione reductase, is identified as the last gene in the ADH transcriptional order, but several pseudogenes for ADH3 have been traced at other chromosomes. The flanking genes outside the ADH genome are similar or identical for all species showing that a larger DNA region has been duplicated and further evolved. However, the only entirely completed ADH genomes are those from primates and rodents.

The latest identified ADH forms, ADH5 (class V) and ADH6 (class VI), are truly different classes and both are very diverged in contrast to ADH3, which is the most conserved class of all ADHs. ADH5 and ADH6 have been identified at the gene and transcriptional levels only, and their functions are still an enigma.},
	number = {1–3},
	urldate = {2013-08-26},
	journal = {Chem. Biol. Interact.},
	author = {Höög, Jan-Olov and Östberg, Linus J.},
	month = may,
	year = {2011},
	keywords = {Alcohol Dehydrogenase, Gene cluster, Isoforms, Mammalian gene family, Protein family},
	pages = {2--7},
	file = {ScienceDirect Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/8HZC5UQC/Höög and Östberg - 2011 - Mammalian alcohol dehydrogenases – A comparative i.pdf:application/pdf;ScienceDirect Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/PJ29XCTX/S0009279711000524.html:text/html}
}

@article{b._hess_p-lincs:_2008,
	title = {P-{LINCS}: {A} {Parallel} {Linear} {Constraint} {Solver} for molecular simulation},
	volume = {4},
	author = {{B. Hess}},
	year = {2008},
	pages = {116--122}
}

@article{wang_pubchem_2017,
	title = {{PubChem} {BioAssay}: 2017 update},
	volume = {45},
	issn = {0305-1048},
	shorttitle = {{PubChem} {BioAssay}},
	doi = {10.1093/nar/gkw1118},
	abstract = {PubChem's BioAssay database (https://pubchem.ncbi.nlm.nih.gov) has served as a public repository for small-molecule and RNAi screening data since 2004 providing open access of its data content to the community. PubChem accepts data submission from worldwide researchers at academia, industry and government agencies. PubChem also collaborates with other chemical biology database stakeholders with data exchange. With over a decade's development effort, it becomes an important information resource supporting drug discovery and chemical biology research. To facilitate data discovery, PubChem is integrated with all other databases at NCBI. In this work, we provide an update for the PubChem BioAssay database describing several recent development including added sources of research data, redesigned BioAssay record page, new BioAssay classification browser and new features in the Upload system facilitating data sharing.},
	number = {Database issue},
	urldate = {2017-03-30},
	journal = {Nucleic Acids Res},
	author = {Wang, Yanli and Bryant, Stephen H. and Cheng, Tiejun and Wang, Jiyao and Gindulyte, Asta and Shoemaker, Benjamin A. and Thiessen, Paul A. and He, Siqian and Zhang, Jian},
	month = jan,
	year = {2017},
	pmid = {27899599},
	pmcid = {PMC5210581},
	pages = {D955--D963},
	file = {PubMed Central Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/HS3RRVPB/Wang et al. - 2017 - PubChem BioAssay 2017 update.pdf:application/pdf}
}

@article{svensson_structural_1998,
	title = {Structural and functional divergence of class {II} alcohol dehydrogenase},
	volume = {251},
	issn = {1432-1033},
	doi = {10.1046/j.1432-1327.1998.2510236.x},
	abstract = {cDNAs coding for class II alcohol dehydrogenase were isolated from a rabbit-liver cDNA library. Deduced amino acid sequences show that isozymic forms of rabbit class II alcohol dehydrogenase exist, with a positional identity of 88.4 \%. A high variability in structure of class II alcohol dehydrogenase between the species is also reflected in function. The rabbit II-1 isozyme shows common characteristics with the human enzyme, but has a lower Km value for ethanol, 4.2 mM. The II-2 isozyme shows restriction for aliphatic alcohols longer than pentanol. For shorter alcohols the II-2 form has similar Km values as the II-1 isozyme, 5.5 mM for ethanol, but is a low activity variant with a 10-fold decrease in kcat values compared with II-1. Nevertheless, II-2 has a higher specificity for benzoquinone than II-1 due to a lower Km value, 80 μM compared with 1 mM, and is in this sense more like the human class II enzyme. In addition a rabbit class III alcohol dehydrogenase cDNA was isolated that encodes a typical class III enzyme/glutathione-dependent formaldehyde dehydrogenase. The finding of isozymic forms of class II alcohol dehydrogenase is in line with the evolution of the system of medium-chain alcohol dehydrogenases with different enzymes, different classes and different isozymes and further underline the complexity of the entire mammalian alcohol dehydrogenase system.},
	language = {en},
	number = {1-2},
	urldate = {2015-11-27},
	journal = {European Journal of Biochemistry},
	author = {Svensson, Stefan and Hedberg, Jesper J. and Höög, Jan-Olov},
	month = jan,
	year = {1998},
	keywords = {Alcohol Dehydrogenase, cDNA sequence, isozyme, recombinant protein, substrate specificity.},
	pages = {236--243}
}

@article{danielsson_enzymogenesis:_1992,
	title = {"{Enzymogenesis}": classical liver alcohol dehydrogenase origin from the glutathione-dependent formaldehyde dehydrogenase line},
	volume = {89},
	issn = {0027-8424},
	shorttitle = {"{Enzymogenesis}"},
	abstract = {Analysis of the activity and structure of lower vertebrate alcohol dehydrogenases reveals that relationships between the classical liver and yeast enzymes need not be continuous. Both the ethanol activity of class I-type alcohol dehydrogenase (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) and the glutathione-dependent formaldehyde activity of the class III-type enzyme [formaldehyde:NAD+ oxidoreductase (glutathione-formylating), EC 1.2.1.1] are present in liver down to at least the stage of bony fishes (cod liver: ethanol activity, 3.4 units/mg of protein in one enzyme; formaldehyde activity, 4.5 units/mg in the major form of another enzyme). Structural analysis of the latter protein reveals it to be a typical class III enzyme, with limited variation from the mammalian form and therefore with stable activity and structure throughout much of the vertebrate lineage. In contrast, the classical alcohol dehydrogenase (the class I enzyme) appears to be the emerging form, first in activity and later also in structure. The class I activity is present already in the piscine line, whereas the overall structural-type enzyme is not observed until amphibians and still more recent vertebrates. Consequently, the class I/III duplicatory origin appears to have arisen from a functional class III form, not a class I form. Therefore, ethanol dehydrogenases from organisms existing before this duplication have origins separate from those leading to the "classical" liver alcohol dehydrogenases. The latter now often occur in isozyme forms from further gene duplications and have a high rate of evolutionary change. The pattern is, however, not simple and we presently find in cod the first evidence for isozymes also within a class III alcohol dehydrogenase. Overall, the results indicate that both of these classes of vertebrate alcohol dehydrogenase are important and suggest a protective metabolic function for the whole enzyme system.},
	language = {eng},
	number = {19},
	journal = {Proc. Natl. Acad. Sci. U.S.A.},
	author = {Danielsson, O. and Jörnvall, H.},
	month = oct,
	year = {1992},
	pmid = {1409630},
	pmcid = {PMC50103},
	keywords = {Alcohol Dehydrogenase, Aldehyde Oxidoreductases, Amino Acid Sequence, Animals, Chromatography, Affinity, Chromatography, DEAE-Cellulose, Fishes, Glutathione, Humans, Isoenzymes, Liver, Molecular Sequence Data, Sequence Homology, Amino Acid},
	pages = {9247--9251}
}

@article{berendsen_gromacs:_1995,
	title = {{GROMACS}: {A} message-passing parallel molecular dynamics implementation},
	volume = {91},
	journal = {Comp. Phys. Comm.},
	author = {Berendsen, H J C and van der Spoel, D and van Drunen, R},
	year = {1995},
	pages = {43--56}
}

@article{soler_effects_2013,
	title = {Effects of {Knots} on {Protein} {Folding} {Properties}},
	volume = {8},
	doi = {10.1371/journal.pone.0074755},
	abstract = {This work explores the impact of knots, knot depth and motif of the threading terminus in protein folding properties (kinetics, thermodynamics and mechanism) via extensive Monte Carlo simulations of lattice models. A knotted backbone has no effect on protein thermodynamic stability but it may affect key aspects of folding kinetics. In this regard, we found clear evidence for a functional advantage of knots: knots enhance kinetic stability because a knotted protein unfolds at a distinctively slower rate than its unknotted counterpart. However, an increase in knot deepness does not necessarily lead to more effective changes in folding properties. In this regard, a terminus with a non-trivial conformation (e.g. hairpin) can have a more dramatic effect in enhancing kinetic stability than knot depth. Nevertheless, our results suggest that the probability of the denatured ensemble to keep knotted is higher for proteins with deeper knots, indicating that knot depth plays a role in determining the topology of the denatured state. Refolding simulations starting from denatured knotted conformations show that not every knot is able to nucleate folding and further indicate that the formation of the knotting loop is a key event in the folding of knotted trefoils. They also show that there are specific native contacts within the knotted core that are crucial to keep a native knotting loop in denatured conformations which otherwise have no detectable structure. The study of the knotting mechanism reveals that the threading of the knotting loop generally occurs towards late folding in conformations that exhibit a significant degree of structural consolidation.},
	number = {9},
	urldate = {2013-09-12},
	journal = {PLoS ONE},
	author = {Soler, Miguel A. and Faísca, Patrícia F. N.},
	month = sep,
	year = {2013},
	pages = {e74755},
	file = {PLoS Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/65MKK9PF/Soler and Faísca - 2013 - Effects of Knots on Protein Folding Properties.html:text/html}
}

@article{krissinel_secondary-structure_2004,
	title = {Secondary-structure matching ({SSM}), a new tool for fast protein structure alignment in three dimensions},
	volume = {D60},
	journal = {Acta Cryst},
	author = {Krissinel, E and Henrick, K},
	year = {2004},
	pages = {2256--2268}
}

@article{f_c_bernstein_protein_1977,
	title = {The {Protein} {Data} {Bank}: {A} {Computer}-based {Archival} {File} {For} {Macromolecular} {Structures}},
	volume = {112},
	journal = {J. of. Mol. Biol.},
	author = {{F C Bernstein} and {T. F. Koetzle} and {G. J. Williams} and {E. E. Meyer Jr} and {M. D. Brice} and {J. R. Rodgers} and {O. Kennard} and {T. Shimanouchi} and {M. Tasumi}},
	year = {1977},
	pages = {535}
}

@article{nordling_molecular_2008,
	title = {Molecular dynamics studies of alpha-helix stability in fibril-forming peptides},
	volume = {22},
	journal = {J Comput Aided Mol Des},
	author = {Nordling, E. and Kallberg, Y. and Johansson, J. and Persson, B},
	year = {2008},
	pages = {53--58}
}

@incollection{eswar_current_2006,
	title = {Current {Protocols} in {Bioinformatics}},
	publisher = {John Wiley \& Sons, Inc},
	author = {Eswar, N and Marti-Renom, M. A. and Webb, B. and Madhusudhan, M. S. and Eramian, D. and Shen, M. and Pieper, U. and Sali, A.},
	year = {2006},
	pages = {Supplement 15, 5.6.1--5.6.30}
}

@article{zhang_template-based_2007,
	title = {Template-based modeling and free modeling by {I}-{TASSER} in {CASP}7},
	volume = {69},
	number = {S8},
	journal = {Proteins: Structure, Function, and Bioinformatics},
	author = {Zhang, Yang},
	year = {2007},
	pages = {108--17}
}

@article{wu_structural_2008,
	title = {Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase {PTGR}2},
	volume = {16},
	issn = {0969-2126},
	doi = {10.1016/j.str.2008.09.007},
	abstract = {PTGR2 catalyzes an NADPH-dependent reduction of the conjugated alpha,beta-unsaturated double bond of 15-keto-PGE(2), a key step in terminal inactivation of prostaglandins and suppression of PPARgamma-mediated adipocyte differentiation. Selective inhibition of PTGR2 may contribute to the improvement of insulin sensitivity with fewer side effects. PTGR2 belongs to the medium-chain dehydrogenase/reductase superfamily. The crystal structures reported here reveal features of the NADPH binding-induced conformational change in a LID motif and a polyproline type II helix which are critical for the reaction. Mutation of Tyr64 and Tyr259 significantly reduces the rate of catalysis but increases the affinity to substrate, confirming the structural observations. Besides targeting cyclooxygenase, indomethacin also inhibits PTGR2 with a binding mode similar to that of 15-keto-PGE(2). The LID motif becomes highly disordered upon the binding of indomethacin, indicating plasticity of the active site. This study has implications for the rational design of inhibitors of PTGR2.},
	language = {eng},
	number = {11},
	journal = {Structure},
	author = {Wu, Yu-Hauh and Ko, Tzu-Ping and Guo, Rey-Ting and Hu, Su-Ming and Chuang, Lee-Ming and Wang, Andrew H.-J.},
	month = nov,
	year = {2008},
	pmid = {19000823},
	keywords = {Alcohol Dehydrogenase, Amino Acid Sequence, Animals, Catalysis, Dinoprostone, Guinea Pigs, Humans, Indomethacin, Kinetics, Mice, Models, Molecular, Molecular Conformation, Molecular Sequence Data, Niacinamide, Protein Binding, Sequence Alignment, Sequence Homology, Amino Acid},
	pages = {1714--1723}
}

@article{skwark_pconsc:_2013,
	title = {{PconsC}: combination of direct information methods and alignments improves contact prediction},
	volume = {29},
	issn = {1367-4811},
	shorttitle = {{PconsC}},
	doi = {10.1093/bioinformatics/btt259},
	abstract = {SUMMARY: Recently, several new contact prediction methods have been published. They use (i) large sets of multiple aligned sequences and (ii) assume that correlations between columns in these alignments can be the results of indirect interaction. These methods are clearly superior to earlier methods when it comes to predicting contacts in proteins. Here, we demonstrate that combining predictions from two prediction methods, PSICOV and plmDCA, and two alignment methods, HHblits and jackhmmer at four different e-value cut-offs, provides a relative improvement of 20\% in comparison with the best single method, exceeding 70\% correct predictions for one contact prediction per residue.
AVAILABILITY: The source code for PconsC along with supplementary data is freely available at http://c.pcons.net/
CONTACT: arne@bioinfo.se
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.},
	language = {eng},
	number = {14},
	journal = {Bioinformatics},
	author = {Skwark, Marcin J. and Abdel-Rehim, Abbi and Elofsson, Arne},
	month = jul,
	year = {2013},
	pmid = {23658418},
	keywords = {Algorithms, Protein Conformation, Proteins, Sequence Alignment, Sequence Analysis, Protein},
	pages = {1815--1816}
}

@article{molotkov_distinct_2002,
	title = {Distinct retinoid metabolic functions for alcohol dehydrogenase genes {Adh}1 and {Adh}4 in protection against vitamin {A} toxicity or deficiency revealed in double null mutant mice},
	volume = {277},
	issn = {0021-9258},
	doi = {10.1074/jbc.M112039200},
	abstract = {The ability of class I alcohol dehydrogenase (ADH1) and class IV alcohol dehydrogenase (ADH4) to metabolize retinol to retinoic acid is supported by genetic studies in mice carrying Adh1 or Adh4 gene disruptions. To differentiate the physiological roles of ADH1 and ADH4 in retinoid metabolism we report here the generation of an Adh1/4 double null mutant mouse and its comparison to single null mutants. We demonstrate that loss of both ADH1 and ADH4 does not have additive effects, either for production of retinoic acid needed for development or for retinol turnover to minimize toxicity. During gestational vitamin A deficiency Adh4 and Adh1/4 mutants exhibit completely penetrant postnatal lethality by day 15 and day 24, respectively, while 60\% of Adh1 mutants survive to adulthood similar to wild-type. Following administration of a 50-mg/kg dose of retinol to examine retinol turnover, Adh1 and Adh1/4 mutants exhibit similar 10-fold decreases in retinoic acid production, whereas Adh4 mutants have only a slight decrease. LD(50) studies indicate a large increase in acute retinol toxicity for Adh1 mutants, a small increase for Adh4 mutants, and an intermediate increase for Adh1/4 mutants. Chronic retinol supplementation during gestation resulted in 65\% postnatal lethality in Adh1 mutants, whereas only approximately 5\% for Adh1/4 and Adh4 mutants. These studies indicate that ADH1 provides considerable protection against vitamin A toxicity, whereas ADH4 promotes survival during vitamin A deficiency, thus demonstrating largely non-overlapping functions for these enzymes in retinoid metabolism.},
	language = {eng},
	number = {16},
	journal = {J. Biol. Chem.},
	author = {Molotkov, Andrei and Deltour, Louise and Foglio, Mario H. and Cuenca, Arnold E. and Duester, Gregg},
	month = apr,
	year = {2002},
	pmid = {11836246},
	pmcid = {PMC2832706},
	keywords = {Alcohol Dehydrogenase, Animals, Chromatography, High Pressure Liquid, Female, Genetic Vectors, Genotype, Heterozygote, Male, Mice, Mice, Transgenic, Models, Genetic, Mutation, Time Factors, Tretinoin, Vitamin A, Vitamin A Deficiency},
	pages = {13804--13811}
}

@article{miinalainen_characterization_2003,
	title = {Characterization of 2-enoyl thioester reductase from mammals. {An} ortholog of {YBR}026p/{MRF}1'p of the yeast mitochondrial fatty acid synthesis type {II}},
	volume = {278},
	issn = {0021-9258},
	doi = {10.1074/jbc.M302851200},
	abstract = {A data base search with YBR026c/MRF1', which encodes trans-2-enoyl thioester reductase of the intramitochondrial fatty acid synthesis (FAS) type II in yeast (Torkko, J. M., Koivuranta, K. T., Miinalainen, I. J., Yagi, A. I., Schmitz, W., Kastaniotis, A. J., Airenne, T. T., Gurvitz, A., and Hiltunen, K. J. (2001) Mol. Cell. Biol. 21, 6243-6253), revealed the clone AA393871 (HsNrbf-1, nuclear receptor binding factor 1) in human EST data bank. Expression of HsNrbf-1, tagged C-terminally with green fluorescent protein, in HeLa cells, resulted in a punctated fluorescence signal, superimposable with the MitoTracker Red dye. Wild-type polypeptide was immunoisolated from the extract of bovine heart mitochondria. Recombinant HsNrbf-1p reduces trans-2-enoyl-CoA to acyl-CoA with chain length from C6 to C16 in an NADPH-dependent manner with preference to medium chain length substrate. Furthermore, expression of HsNRBF-1 in the ybr026cDelta yeast strain restored mitochondrial respiratory function allowing growth on glycerol. These findings provide evidence that Nrbf-1ps act as a mitochondrial 2-enoyl thioester reductase, and mammalian cells may possess bacterial type fatty acid synthetase (FAS type II) in mitochondria, in addition to FAS type I in the cytoplasm.},
	language = {eng},
	number = {22},
	journal = {J. Biol. Chem.},
	author = {Miinalainen, Ilkka J. and Chen, Zhi-Jun and Torkko, Juha M. and Pirilä, Päivi L. and Sormunen, Raija T. and Bergmann, Ulrich and Qin, Yong-Mei and Hiltunen, J. Kalervo},
	month = may,
	year = {2003},
	pmid = {12654921},
	keywords = {Amino Acid Sequence, Animals, Base Sequence, Cattle, DNA Primers, Fatty Acid Desaturases, HeLa Cells, Humans, Microscopy, Fluorescence, Mitochondria, Heart, Molecular Sequence Data, NADH, NADPH Oxidoreductases, Oxidoreductases Acting on CH-CH Group Donors, Saccharomyces cerevisiae, Sequence Homology, Amino Acid},
	pages = {20154--20161}
}

@article{ostberg_computational_2016,
	title = {Computational studies of human class {V} alcohol dehydrogenase - the odd sibling},
	volume = {17},
	issn = {1471-2091},
	doi = {10.1186/s12858-016-0072-y},
	abstract = {All known attempts to isolate and characterize mammalian class V alcohol dehydrogenase (class V ADH), a member of the large ADH protein family, at the protein level have failed. This indicates that the class V ADH protein is not stable in a non-cellular environment, which is in contrast to all other human ADH enzymes. In this report we present evidence, supported with results from computational analyses performed in combination with earlier in vitro studies, why this ADH behaves in an atypical way.},
	urldate = {2017-01-19},
	journal = {BMC Biochemistry},
	author = {Östberg, Linus J. and Persson, Bengt and Höög, Jan-Olov},
	year = {2016},
	keywords = {Alcohol Dehydrogenase, Mutational pressure, Pseudoenzyme, Sequence analysis, Structural calculations},
	pages = {16}
}

@article{wu_protein_2003,
	title = {The {Protein} {Information} {Resource}},
	volume = {31},
	issn = {0305-1048},
	doi = {10.1093/nar/gkg040},
	number = {1},
	urldate = {2017-03-24},
	journal = {Nucleic Acids Res},
	author = {Wu, Cathy H. and Yeh, Lai-Su L. and Huang, Hongzhan and Arminski, Leslie and Castro-Alvear, Jorge and Chen, Yongxing and Hu, Zhangzhi and Kourtesis, Panagiotis and Ledley, Robert S. and Suzek, Baris E. and Vinayaka, C. R. and Zhang, Jian and Barker, Winona C.},
	month = jan,
	year = {2003},
	pages = {345--347},
	file = {Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/P7GFEQ79/Wu et al. - 2003 - The Protein Information Resource.pdf:application/pdf;Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/IHKTKJM3/gkg040.html:text/html}
}

@article{persson_characteristics_1991,
	title = {Characteristics of short-chain alcohol dehydrogenases and related enzymes},
	volume = {200},
	issn = {0014-2956},
	abstract = {Different short-chain dehydrogenases are distantly related, constituting a protein family now known from at least 20 separate enzymes characterized, but with extensive differences, especially in the C-terminal third of their sequences. Many of the first known members were prokaryotic, but recent additions include mammalian enzymes from placenta, liver and other tissues, including 15-hydroxyprostaglandin, 17 beta-hydroxysteroid and 11 beta-hydroxysteroid dehydrogenases. In addition, species variants, isozyme-like multiplicities and mutants have been reported for several of the structures. Alignments of the different enzymes reveal large homologous parts, with clustered similarities indicating regions of special functional/structural importance. Several of these derive from relationships within a common type of coenzyme-binding domain, but central-chain patterns of similarity go beyond this domain. Total residue identities between enzyme pairs are typically around 25\%, but single forms deviate more or less (14-58\%). Only six of the 250-odd residues are strictly conserved and seven more are conserved in all but single cases. Over one third of the conserved residues are glycine, showing the importance of conformational and spatial restrictions. Secondary structure predictions, residue distributions and hydrophilicity profiles outline a common, N-terminal coenzyme-binding domain similar to that of other dehydrogenases, and a C-terminal domain with unique segments and presumably individual functions in each case. Strictly conserved residues of possible functional interest are limited, essentially only three polar residues. Asp64, Tyr152 and Lys156 (in the numbering of Drosophila alcohol dehydrogenase), but no histidine or cysteine residue like in the completely different, classical medium-chain alcohol dehydrogenase family. Asp64 is in the suggested coenzyme-binding domain, whereas Tyr152 and Lys156 are close to the center of the protein chain, at a putative inter-domain, active-site segment. Consequently, the overall comparisons suggest the possibility of related mechanisms and domain properties for different members of the short-chain family.},
	language = {eng},
	number = {2},
	journal = {Eur. J. Biochem.},
	author = {Persson, B. and Krook, M. and Jörnvall, H.},
	month = sep,
	year = {1991},
	pmid = {1889416},
	keywords = {Alcohol Dehydrogenase, Amino Acid Sequence, Binding Sites, Coenzymes, Isoenzymes, Molecular Sequence Data, Sequence Alignment, Sequence Homology, Nucleic Acid},
	pages = {537--543}
}

@article{ferrari_soft_2004,
	title = {Soft {Docking} and multiple receptor conformation in virtual screening},
	volume = {47},
	journal = {J. Med. Chem},
	author = {Ferrari, A M and Wei, B Q and Costantino, L and Shoichet, B K},
	year = {2004},
	pages = {5076--5084}
}

@article{hellgren_enrichment_2010,
	title = {Enrichment of ligands with molecular dockings and subsequent characterization for human alcohol dehydrogenase},
	volume = {67},
	number = {17},
	journal = {Cell. Mol. Life. Sci.},
	author = {Hellgren, Mikko and Carlsson, Jonas and Östberg, Linus J and Staab, Claudia A and Persson, Bengt and Höög, Jan-Olov},
	year = {2010},
	pages = {3005--15}
}

@article{kleiger_gxxxg_2002,
	title = {{GXXXG} and {GXXXA} {Motifs} {Stabilize} {FAD} and {NAD}({P})-binding {Rossmann} {Folds} {Through} {C$\alpha$}–{H}⋯{O} {Hydrogen} {Bonds} and van der {Waals} {Interactions}},
	volume = {323},
	issn = {0022-2836},
	doi = {10.1016/S0022-2836(02)00885-9},
	abstract = {Here we present evidence that domains in soluble proteins containing either the GXXXG or GXXXA motif are stabilized by the interaction of a $\beta$-strand with the following $\alpha$-helix. As an example, we characterized a $\beta$-strand–helix interaction from the FAD or NAD(P)-binding Rossmann fold. The Rossmann fold is one of the three most highly represented folds in the Protein Data Bank (PDB). A subset of the proteins that adopt the Rossmann fold also bind to nucleotide cofactors such as FAD and NAD(P) and function as oxidoreductases. These Rossmann folds can often be identified by the short amino acid sequence motif, GX1–2GXXG. Here, we present evidence that in addition to this sequence motif, Rossmann folds that bind FAD and NAD(P) also typically contain either GXXXG or GXXXA motifs, where the first glycyl residue of these motifs and the third glycyl residue of the GX1–2GXXG motif are the same residue. These two motifs appear to stabilize the Rossmann fold: the first glycyl residue of either the GXXXG or GXXXA motif contacts the carbonyl oxygen atom from the first glycyl residue of the GX1–2GXXG motif consistent with the formation of a C$\alpha$–H⋯O hydrogen bond. In addition, both the glycyl and alanyl residues of the GXXXG or GXXXA motifs form van der Waals interactions with either a valine or isoleucine residue located either seven or eight residues further back along the polypeptide chain from the first glycine of the GXXXG or GXXXA motifs. Therefore, we combine both the GX1–2GXXG and GXXXG/A motifs into an extended motif, V/IXGX1–2GXXGXXXG/A, that is more strongly indicative than previously described motifs of Rossmann folds that bind FAD or NAD(P). The V/IXGX1–2GXXGXXXG/A motif can be used to search genomic sequence data and to annotate the function of proteins containing the motif as oxidoreductases, including proteins of previously unknown function.},
	number = {1},
	urldate = {2017-03-06},
	journal = {Journal of Molecular Biology},
	author = {Kleiger, Gary and Eisenberg, David},
	month = oct,
	year = {2002},
	keywords = {FAD-binding, hydrogen bond, NAD(P)-binding, Rossmann fold, sequence motif},
	pages = {69--76},
	file = {ScienceDirect Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/II98RM8N/Kleiger and Eisenberg - 2002 - GXXXG and GXXXA Motifs Stabilize FAD and NAD(P)-bi.pdf:application/pdf;ScienceDirect Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/BMXKZUVC/Kleiger and Eisenberg - 2002 - GXXXG and GXXXA Motifs Stabilize FAD and NAD(P)-bi.html:text/html}
}

@article{abagyan_biased_1994,
	title = {Biased probability {Monte} {Carlo} conformational searches and electrostatic calculations for peptides and proteins},
	volume = {235},
	journal = {J. Mol. Biol.},
	author = {Abagyan, R and Totrov, M},
	year = {1994},
	pages = {983--1002}
}

@article{lassmann_kalign2:_2009,
	title = {Kalign2: high-performance multiple alignment of protein and nucleotide sequences allowing external features},
	volume = {37},
	issn = {1362-4962},
	shorttitle = {Kalign2},
	doi = {10.1093/nar/gkn1006},
	abstract = {In the growing field of genomics, multiple alignment programs are confronted with ever increasing amounts of data. To address this growing issue we have dramatically improved the running time and memory requirement of Kalign, while maintaining its high alignment accuracy. Kalign version 2 also supports nucleotide alignment, and a newly introduced extension allows for external sequence annotation to be included into the alignment procedure. We demonstrate that Kalign2 is exceptionally fast and memory-efficient, permitting accurate alignment of very large numbers of sequences. The accuracy of Kalign2 compares well to the best methods in the case of protein alignments while its accuracy on nucleotide alignments is generally superior. In addition, we demonstrate the potential of using known or predicted sequence annotation to improve the alignment accuracy. Kalign2 is freely available for download from the Kalign web site (http://msa.sbc.su.se/).},
	language = {eng},
	number = {3},
	journal = {Nucleic Acids Res.},
	author = {Lassmann, Timo and Frings, Oliver and Sonnhammer, Erik L. L.},
	month = feb,
	year = {2009},
	pmid = {19103665},
	pmcid = {PMC2647288},
	keywords = {Reproducibility of Results, Sequence Alignment, Sequence Analysis, Protein, Sequence Analysis, RNA, Software, Time Factors},
	pages = {858--865}
}

@book{noauthor_molsoft_2012,
	title = {Molsoft {L}.{L}.{C}.: {Publications}},
	year = {2012}
}

@article{hu_identification_2002,
	title = {Identification and characterization of a novel {Nogo}-interacting mitochondrial protein ({NIMP})},
	volume = {81},
	issn = {0022-3042},
	abstract = {Nogo is a potent inhibitor of regeneration following spinal cord injury. To develop a better understanding of the mechanisms responsible for regenerative failure we used a yeast two-hybrid approach to try and identify proteins that interact with Nogo. We identified a novel mitochondrial protein designated Nogo-interacting mitochondrial protein (NIMP) in a screen of an adult human brain cDNA library. This interaction was confirmed by co-immunoprecipitation in both brain tissue (endogenous) and transfected HEK293T cells (overexpressed). In support of these studies we demonstrate that Nogo interacts with the UQCRC1 and UQCRC2 components of complex III, within the mitochondrial respiratory chain. The mitochondrial localization of NIMP was evidenced by confocal image analysis and western blot analysis of isolated mitochondria. NIMP is highly conserved and ubiquitously expressed in mitochondria-enriched tissues. Within the CNS, NIMP-like immunoreactivity is present in neurons and astrocytes. These data suggest that NIMP is a novel mitochondrial protein that interacts with Nogo. The interaction of Nogo with mitochondrial proteins may provide insight into the mechanisms for Nogo-induced inhibition of neurite growth.},
	language = {eng},
	number = {1},
	journal = {J. Neurochem.},
	author = {Hu, Wen-Hui and Hausmann, Oliver N. and Yan, Ming-Shan and Walters, Winston M. and Wong, Paul K. Y. and Bethea, John R.},
	month = apr,
	year = {2002},
	pmid = {12067236},
	keywords = {Animals, Carrier Proteins, Cattle, Cell Line, Conserved Sequence, COS Cells, Electron Transport Complex III, Humans, Macromolecular Substances, Mice, Mitochondria, Mitochondrial Proteins, Molecular Sequence Data, Myelin Proteins, Nerve Regeneration, Nogo Proteins, Organ Specificity, Protein Binding, Protein Subunits, Recombinant Fusion Proteins, RNA, Messenger, Sequence Alignment, Sequence Homology, Amino Acid, Two-Hybrid System Techniques},
	pages = {36--45}
}

@article{desiere_peptideatlas_2006,
	title = {The {PeptideAtlas} project},
	volume = {34},
	issn = {0305-1048, 1362-4962},
	doi = {10.1093/nar/gkj040},
	abstract = {The completion of the sequencing of the human genome and the concurrent, rapid development of high-throughput proteomic methods have resulted in an increasing need for automated approaches to archive proteomic data in a repository that enables the exchange of data among researchers and also accurate integration with genomic data. PeptideAtlas (http://www.peptideatlas.org/) addresses these needs by identifying peptides by tandem mass spectrometry (MS/MS), statistically validating those identifications and then mapping identified sequences to the genomes of eukaryotic organisms. A meaningful comparison of data across different experiments generated by different groups using different types of instruments is enabled by the implementation of a uniform analytic process. This uniform statistical validation ensures a consistent and high-quality set of peptide and protein identifications. The raw data from many diverse proteomic experiments are made available in the associated PeptideAtlas repository in several formats. Here we present a summary of our process and details about the Human, Drosophila and Yeast PeptideAtlas builds.},
	language = {en},
	number = {suppl 1},
	urldate = {2014-12-11},
	journal = {Nucl. Acids Res.},
	author = {Desiere, Frank and Deutsch, Eric W. and King, Nichole L. and Nesvizhskii, Alexey I. and Mallick, Parag and Eng, Jimmy and Chen, Sharon and Eddes, James and Loevenich, Sandra N. and Aebersold, Ruedi},
	month = jan,
	year = {2006},
	pmid = {16381952},
	pages = {D655--D658}
}

@article{levinthal_how_1969,
	title = {How to fold graciously},
	journal = {Mossbauer Spectroscopy in Biological Systems},
	author = {Levinthal, Cyrus},
	year = {1969},
	pages = {22}
}

@incollection{bolton_pubchem:_2008,
	title = {{PubChem}: {Integrated} {Platform} of {Small} {Molecules} and {Biological} {Activities}},
	volume = {4},
	booktitle = {Annual {Reports} in {Computational} {Chemistry}},
	author = {Bolton, E and Wang, Y and Thiessen, P A and Bryant, S H},
	month = apr,
	year = {2008}
}

@article{wierenga_prediction_1986,
	title = {Prediction of the occurrence of the {ADP}-binding $\beta$$\alpha$$\beta$-fold in proteins, using an amino acid sequence fingerprint},
	volume = {187},
	issn = {0022-2836},
	doi = {10.1016/0022-2836(86)90409-2},
	abstract = {An amino acid sequence “fingerprint” has been derived that can be used to test if a particular sequence will fold into a$\beta$$\alpha$$\beta$-unit with ADP-binding properties. It was deduced from a careful analysis of the known three-dimensional structures of ADP-binding $\beta$$\alpha$$\beta$-folds. This fingerprint is in fact a set of 11 rules describing the type of amino acid that should occur at a specific position in a peptide fragment. The total length of this fingerprint varies between 29 and 31 residues. By checking against all possible sequences in a database, it appeared that every peptide, which exactly follows this fingerprint, does indeed fold into an ADP-binding $\beta$$\alpha$$\beta$-unit.},
	number = {1},
	urldate = {2017-03-06},
	journal = {Journal of Molecular Biology},
	author = {Wierenga, Rik K. and Terpstra, Peter and Hol, Wim G. J.},
	month = jan,
	year = {1986},
	pages = {101--107}
}

@article{hedlund_subdivision_2010,
	title = {Subdivision of the {MDR} superfamily of medium-chain dehydrogenases/reductases through iterative hidden {Markov} model refinement},
	volume = {11},
	issn = {1471-2105},
	doi = {10.1186/1471-2105-11-534},
	abstract = {BACKGROUND: The Medium-chain Dehydrogenases/Reductases (MDR) form a protein superfamily whose size and complexity defeats traditional means of subclassification; it currently has over 15000 members in the databases, the pairwise sequence identity is typically around 25\%, there are members from all kingdoms of life, the chain-lengths vary as does the oligomericity, and the members are partaking in a multitude of biological processes. There are profile hidden Markov models (HMMs) available for detecting MDR superfamily members, but none for determining which MDR family each protein belongs to. The current torrential influx of new sequence data enables elucidation of more and more protein families, and at an increasingly fine granularity. However, gathering good quality training data usually requires manual attention by experts and has therefore been the rate limiting step for expanding the number of available models.
RESULTS: We have developed an automated algorithm for HMM refinement that produces stable and reliable models for protein families. This algorithm uses relationships found in data to generate confident seed sets. Using this algorithm we have produced HMMs for 86 distinct MDR families and 34 of their subfamilies which can be used in automated annotation of new sequences. We find that MDR forms with 2 Zn2+ ions in general are dehydrogenases, while MDR forms with no Zn2+ in general are reductases. Furthermore, in Bacteria MDRs without Zn2+ are more frequent than those with Zn2+, while the opposite is true for eukaryotic MDRs, indicating that Zn2+ has been recruited into the MDR superfamily after the initial life kingdom separations. We have also developed a web site http://mdr-enzymes.org that provides textual and numeric search against various characterised MDR family properties, as well as sequence scan functions for reliable classification of novel MDR sequences.
CONCLUSIONS: Our method of refinement can be readily applied to create stable and reliable HMMs for both MDR and other protein families, and to confidently subdivide large and complex protein superfamilies. HMMs created using this algorithm correspond to evolutionary entities, making resolution of overlapping models straightforward. The implementation and support scripts for running the algorithm on computer clusters are available as open source software, and the database files underlying the web site are freely downloadable. The web site also makes our findings directly useful also for non-bioinformaticians.},
	language = {eng},
	journal = {BMC Bioinformatics},
	author = {Hedlund, Joel and Jörnvall, Hans and Persson, Bengt},
	year = {2010},
	pmid = {20979641},
	keywords = {Algorithms, Cluster Analysis, Computational Biology, Databases, Protein, Markov Chains, Oxidoreductases, Sequence Alignment},
	pages = {534}
}

@article{simons_assembly_1997,
	title = {Assembly of protein tertiary structures from fragments with similar local sequences using simulated annealing and {Bayesian} scoring functions},
	volume = {268},
	issn = {0022-2836},
	doi = {10.1006/jmbi.1997.0959},
	abstract = {We explore the ability of a simple simulated annealing procedure to assemble native-like structures from fragments of unrelated protein structures with similar local sequences using Bayesian scoring functions. Environment and residue pair specific contributions to the scoring functions appear as the first two terms in a series expansion for the residue probability distributions in the protein database; the decoupling of the distance and environment dependencies of the distributions resolves the major problems with current database-derived scoring functions noted by Thomas and Dill. The simulated annealing procedure rapidly and frequently generates native-like structures for small helical proteins and better than random structures for small beta sheet containing proteins. Most of the simulated structures have native-like solvent accessibility and secondary structure patterns, and thus ensembles of these structures provide a particularly challenging set of decoys for evaluating scoring functions. We investigate the effects of multiple sequence information and different types of conformational constraints on the overall performance of the method, and the ability of a variety of recently developed scoring functions to recognize the native-like conformations in the ensembles of simulated structures.},
	language = {eng},
	number = {1},
	journal = {J. Mol. Biol.},
	author = {Simons, K. T. and Kooperberg, C. and Huang, E. and Baker, D.},
	month = apr,
	year = {1997},
	pmid = {9149153},
	keywords = {Bayes Theorem, Computer Simulation, Databases, Factual, Models, Molecular, Models, Statistical, Peptide Fragments, Protein Folding, Proteins, Protein Structure, Tertiary, Sequence Homology, Amino Acid},
	pages = {209--225}
}

@article{altschul_basic_1990,
	title = {Basic local alignment search tool},
	volume = {215},
	issn = {0022-2836},
	doi = {10.1016/S0022-2836(05)80360-2},
	abstract = {A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score. Recent mathematical results on the stochastic properties of MSP scores allow an analysis of the performance of this method as well as the statistical significance of alignments it generates. The basic algorithm is simple and robust; it can be implemented in a number of ways and applied in a variety of contexts including straightforward DNA and protein sequence database searches, motif searches, gene identification searches, and in the analysis of multiple regions of similarity in long DNA sequences. In addition to its flexibility and tractability to mathematical analysis, BLAST is an order of magnitude faster than existing sequence comparison tools of comparable sensitivity.},
	language = {eng},
	number = {3},
	journal = {J. Mol. Biol.},
	author = {Altschul, S. F. and Gish, W. and Miller, W. and Myers, E. W. and Lipman, D. J.},
	month = oct,
	year = {1990},
	pmid = {2231712},
	keywords = {Algorithms, Amino Acid Sequence, Base Sequence, Databases, Factual, Mutation, Sensitivity and Specificity, Sequence Homology, Nucleic Acid, Software},
	pages = {403--410}
}

@article{staab_medium-_2008,
	title = {Medium- and short-chain dehydrogenase/reductase gene and protein families : {Dual} functions of alcohol dehydrogenase 3: implications with focus on formaldehyde dehydrogenase and {S}-nitrosoglutathione reductase activities},
	volume = {65},
	issn = {1420-9071},
	shorttitle = {Medium- and short-chain dehydrogenase/reductase gene and protein families},
	doi = {10.1007/s00018-008-8592-2},
	abstract = {Alcohol dehydrogenase 3 (ADH3) is highly conserved, ubiquitously expressed in mammals and involved in essential cellular pathways. A large active site pocket entails special substrate specificities: shortchain alcohols are poor substrates, while medium-chain alcohols and particularly the glutathione adducts S-hydroxymethylglutathione (HMGSH) and S-nitrosoglutathione (GSNO) are efficiently converted under concomitant use of NAD(+)/NADH. By oxidation of HMGSH, the spontaneous glutathione adduct of formaldehyde, ADH3 is implicated in the detoxification of formaldehyde. Through the GSNO reductase activity, ADH3 can affect the transnitrosation equilibrium between GSNO and S-nitrosated proteins, arguing for an important role in NO homeostasis. Recent findings suggest that ADH3-mediated GSNO reduction and subsequent product formation responds to redox states in terms of NADH availability and glutathione levels. Finally, a dual function of ADH3 is discussed in view of its potential implications for asthma.},
	language = {eng},
	number = {24},
	journal = {Cell. Mol. Life Sci.},
	author = {Staab, C. A. and Hellgren, M. and Höög, J.-O.},
	month = dec,
	year = {2008},
	pmid = {19011746},
	keywords = {Alcohol Dehydrogenase, Aldehyde Oxidoreductases, Animals, Humans, Multigene Family, Organ Specificity, Oxidation-Reduction, S-nitrosoglutathione},
	pages = {3950--3960}
}

@article{carlsson_folding_2010,
	title = {A folding study on {IAPP} ({Islet} {Amyloid} {Polypeptide}) using molecular dynamics simulations},
	journal = {Manuscript},
	author = {Carlsson, J. and Shariatpanahi, A. V. and Schultz, S. W. and Westermark, G. T. and Persson, B},
	year = {2010}
}

@article{carlsson_structural_2011,
	title = {A structural model of human steroid 11-beta-hydroxylase, {CYP}11B1, used to predict consequences of mutations},
	journal = {Manuscript},
	author = {Carlsson, J. and Wedell, A. and Persson, B.},
	year = {2011}
}

@article{boratyn_domain_2012,
	title = {Domain enhanced lookup time accelerated {BLAST}},
	volume = {7},
	issn = {1745-6150},
	doi = {10.1186/1745-6150-7-12},
	abstract = {BACKGROUND: BLAST is a commonly-used software package for comparing a query sequence to a database of known sequences; in this study, we focus on protein sequences. Position-specific-iterated BLAST (PSI-BLAST) iteratively searches a protein sequence database, using the matches in round i to construct a position-specific score matrix (PSSM) for searching the database in round i + 1. Biegert and Söding developed Context-sensitive BLAST (CS-BLAST), which combines information from searching the sequence database with information derived from a library of short protein profiles to achieve better homology detection than PSI-BLAST, which builds its PSSMs from scratch.
RESULTS: We describe a new method, called domain enhanced lookup time accelerated BLAST (DELTA-BLAST), which searches a database of pre-constructed PSSMs before searching a protein-sequence database, to yield better homology detection. For its PSSMs, DELTA-BLAST employs a subset of NCBI's Conserved Domain Database (CDD). On a test set derived from ASTRAL, with one round of searching, DELTA-BLAST achieves a ROC5000 of 0.270 vs. 0.116 for CS-BLAST. The performance advantage diminishes in iterated searches, but DELTA-BLAST continues to achieve better ROC scores than CS-BLAST.
CONCLUSIONS: DELTA-BLAST is a useful program for the detection of remote protein homologs. It is available under the "Protein BLAST" link at http://blast.ncbi.nlm.nih.gov.},
	language = {eng},
	journal = {Biol. Direct},
	author = {Boratyn, Grzegorz M. and Schäffer, Alejandro A. and Agarwala, Richa and Altschul, Stephen F. and Lipman, David J. and Madden, Thomas L.},
	month = apr,
	year = {2012},
	pmid = {22510480},
	pmcid = {PMC3438057},
	keywords = {Algorithms, Computational Biology, Databases, Protein, Internet, Protein Structure, Tertiary, Reproducibility of Results, ROC Curve, Search Engine, Sensitivity and Specificity, Sequence Alignment, Sequence Analysis, Protein, Sequence Homology, Amino Acid, Software, Time Factors},
	pages = {12}
}

@article{estonius_distribution_1993,
	title = {Distribution of alcohol and sorbitol dehydrogenases. {Assessment} of {mRNA} species in mammalian tissues},
	volume = {215},
	issn = {0014-2956},
	abstract = {The tissue distribution of mRNA of alcohol dehydrogenases of classes I, II and III, and sorbitol dehydrogenase, was studied. mRNA from 19 different rat tissues was purified and analyzed by Northern blots, utilizing cDNA probes specific for the four dehydrogenases. Class-I alcohol-dehydrogenase mRNA was shown to be of widespread occurrence, detectable in all tissues including brain, but with pronounced differences in amounts. Hybridization revealed the pattern of occurrence of class-II alcohol-dehydrogenase mRNA to be unique, with transcripts only in the liver, duodenum, kidney, stomach, spleen and testis. Abundant levels of class-III alcohol-dehydrogenase (glutathione-dependent formaldehyde dehydrogenase) mRNA were present in all tissues analyzed, reflecting the general need for scavenging of formaldehyde in physiological cytoprotection. Sorbitol dehydrogenase mRNA was detected in all tissues except small intestine, in agreement with sorbitol resorbtion by passive diffusion in this tissue. In addition, evidence for a sex-specific expression, in the liver, of class-II alcohol dehydrogenase was obtained.},
	language = {eng},
	number = {2},
	journal = {Eur. J. Biochem.},
	author = {Estonius, M. and Danielsson, O. and Karlsson, C. and Persson, H. and Jörnvall, H. and Höög, J-O},
	month = jul,
	year = {1993},
	pmid = {8344317},
	keywords = {Alcohol Dehydrogenase, Amino Acid Sequence, Animals, Base Sequence, Blotting, Northern, DNA, Female, L-Iditol 2-Dehydrogenase, Male, Molecular Sequence Data, Nucleic Acid Hybridization, Rats, Rats, Sprague-Dawley, RNA, Messenger, Tissue Distribution, Transcription, Genetic},
	pages = {497--503}
}

@book{steinbach_introduction_2005,
	title = {Introduction to macromolecular simulation},
	author = {Steinbach, Peter J},
	month = aug,
	year = {2005},
	note = {Published: Retrieved January 23, 2010 from http://cmm.cit.nih.gov/intro\_simulation}
}

@article{moult_critical_2011,
	title = {Critical assessment of methods of protein structure prediction ({CASP})—round {IX}},
	volume = {79},
	number = {S10},
	journal = {Proteins: Structure, Function, and Bioinformatics},
	author = {Moult, John and Fidelis, Krzysztof and Kryshtafovych, Andriy and Tramontano, Anna},
	year = {2011},
	pages = {1--207}
}

@article{nemethy_energy_1992,
	title = {Energy parameters in polypeptides. 10. {Improved} geometrical parameters and nonbonded interactions for use in the {ECEPP}/3 algorithm, with application to proline-containing peptides},
	volume = {96},
	number = {15},
	journal = {J. Phys. Chem.},
	author = {Nemethy, George and Gibson, Kenneth D and Palmer, Kathleen A and Yoon, Chang No and Paterlini, Germana and Zagari, Adriana and Rumsey, Shirley and Scheraga, Harold A},
	year = {1992},
	pages = {6472--6484}
}

@book{baldi_bioinformatics:_1998,
	address = {Cambridge},
	title = {Bioinformatics: the {Machine} {Learning} {Aproach}},
	publisher = {MIT Press},
	author = {Baldi, Pierre and Brunak, Søren},
	year = {1998}
}

@article{ncbi_resource_coordinators_database_2016,
	title = {Database resources of the {National} {Center} for {Biotechnology} {Information}},
	volume = {44},
	issn = {0305-1048},
	doi = {10.1093/nar/gkv1290},
	abstract = {The National Center for Biotechnology Information (NCBI) provides a large suite of online resources for biological information and data, including the GenBank® nucleic acid sequence database and the PubMed database of citations and abstracts for published life science journals. Additional NCBI resources focus on literature (PubMed Central (PMC), Bookshelf and PubReader), health (ClinVar, dbGaP, dbMHC, the Genetic Testing Registry, HIV-1/Human Protein Interaction Database and MedGen), genomes (BioProject, Assembly, Genome, BioSample, dbSNP, dbVar, Epigenomics, the Map Viewer, Nucleotide, Probe, RefSeq, Sequence Read Archive, the Taxonomy Browser and the Trace Archive), genes (Gene, Gene Expression Omnibus (GEO), HomoloGene, PopSet and UniGene), proteins (Protein, the Conserved Domain Database (CDD), COBALT, Conserved Domain Architecture Retrieval Tool (CDART), the Molecular Modeling Database (MMDB) and Protein Clusters) and chemicals (Biosystems and the PubChem suite of small molecule databases). The Entrez system provides search and retrieval operations for most of these databases. Augmenting many of the web applications are custom implementations of the BLAST program optimized to search specialized datasets. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.},
	number = {Database issue},
	urldate = {2017-03-24},
	journal = {Nucleic Acids Res},
	author = {{NCBI Resource Coordinators}},
	month = jan,
	year = {2016},
	pmid = {26615191},
	pmcid = {PMC4702911},
	pages = {D7--D19},
	file = {PubMed Central Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/NAGMB8KA/2016 - Database resources of the National Center for Biot.pdf:application/pdf}
}

@article{porte_three-dimensional_2009,
	title = {Three-dimensional structure and enzymatic function of proapoptotic human p53-inducible quinone oxidoreductase {PIG}3},
	volume = {284},
	issn = {1083-351X},
	doi = {10.1074/jbc.M109.001800},
	abstract = {Tumor suppressor p53 regulates the expression of p53-induced genes (PIG) that trigger apoptosis. PIG3 or TP53I3 is the only known member of the medium chain dehydrogenase/reductase superfamily induced by p53 and is used as a proapoptotic marker. Although the participation of PIG3 in the apoptotic pathway is proven, the protein and its mechanism of action were never characterized. We analyzed human PIG3 enzymatic function and found NADPH-dependent reductase activity with ortho-quinones, which is consistent with the classification of PIG3 in the quinone oxidoreductase family. However, the activity is much lower than that of zeta-crystallin, a better known quinone oxidoreductase. In addition, we report the crystallographic structure of PIG3, which allowed the identification of substrate- and cofactor-binding sites, with residues fully conserved from bacteria to human. Tyr-59 in zeta-crystallin (Tyr-51 in PIG3) was suggested to participate in the catalysis of quinone reduction. However, kinetics of Tyr/Phe and Tyr/Ala mutants of both enzymes demonstrated that the active site Tyr is not catalytic but may participate in substrate binding, consistent with a mechanism based on propinquity effects. It has been proposed that PIG3 contribution to apoptosis would be through oxidative stress generation. We found that in vitro activity and in vivo overexpression of PIG3 accumulate reactive oxygen species. Accordingly, an inactive PIG3 mutant (S151V) did not produce reactive oxygen species in cells, indicating that enzymatically active protein is necessary for this function. This supports that PIG3 action is through oxidative stress produced by its enzymatic activity and provides essential knowledge for eventual control of apoptosis.},
	language = {eng},
	number = {25},
	journal = {J. Biol. Chem.},
	author = {Porté, Sergio and Valencia, Eva and Yakovtseva, Evgenia A. and Borràs, Emma and Shafqat, Naeem and Debreczeny, Judit E. and Pike, Ashley C. W. and Oppermann, Udo and Farrés, Jaume and Fita, Ignacio and Parés, Xavier},
	month = jun,
	year = {2009},
	pmid = {19349281},
	pmcid = {PMC2719357},
	keywords = {Amino Acid Sequence, apoptosis, Binding Sites, Catalytic Domain, Crystallography, X-Ray, Humans, Intracellular Signaling Peptides and Proteins, In Vitro Techniques, Kinetics, Models, Molecular, Molecular Sequence Data, Mutagenesis, Site-Directed, NADP, Phylogeny, Protein Structure, Quaternary, Proto-Oncogene Proteins, reactive oxygen species, Recombinant Proteins, Sequence Homology, Amino Acid, Tumor Suppressor Protein p53, Tyrosine},
	pages = {17194--17205}
}

@misc{noauthor_research_nodate,
	title = {The {Research} {Collaboratory} for {Structural} {Bioinformatics} {PDB}},
	url = {http://www.rcsb.org/pdb/}
}

@article{yang_paml_2007,
	title = {{PAML} 4: phylogenetic analysis by maximum likelihood},
	volume = {24},
	issn = {0737-4038},
	shorttitle = {{PAML} 4},
	doi = {10.1093/molbev/msm088},
	abstract = {PAML, currently in version 4, is a package of programs for phylogenetic analyses of DNA and protein sequences using maximum likelihood (ML). The programs may be used to compare and test phylogenetic trees, but their main strengths lie in the rich repertoire of evolutionary models implemented, which can be used to estimate parameters in models of sequence evolution and to test interesting biological hypotheses. Uses of the programs include estimation of synonymous and nonsynonymous rates (d(N) and d(S)) between two protein-coding DNA sequences, inference of positive Darwinian selection through phylogenetic comparison of protein-coding genes, reconstruction of ancestral genes and proteins for molecular restoration studies of extinct life forms, combined analysis of heterogeneous data sets from multiple gene loci, and estimation of species divergence times incorporating uncertainties in fossil calibrations. This note discusses some of the major applications of the package, which includes example data sets to demonstrate their use. The package is written in ANSI C, and runs under Windows, Mac OSX, and UNIX systems. It is available at -- (http://abacus.gene.ucl.ac.uk/software/paml.html).},
	language = {eng},
	number = {8},
	journal = {Mol. Biol. Evol.},
	author = {Yang, Ziheng},
	month = aug,
	year = {2007},
	pmid = {17483113},
	keywords = {Animals, Computer Simulation, Genetic Variation, Likelihood Functions, Models, Genetic, Phylogeny, Selection, Genetic, Software, Species Specificity},
	pages = {1586--1591}
}

@article{ohta_synonymous_1995,
	title = {Synonymous and nonsynonymous substitutions in mammalian genes and the nearly neutral theory},
	volume = {40},
	issn = {0022-2844},
	abstract = {The nearly neutral theory of molecular evolution predicts larger generation-time effects for synonymous than for nonsynonymous substitutions. This prediction is tested using the sequences of 49 single-copy genes by calculating the average and variance of synonymous and nonsynonymous substitutions in mammalian star phylogenies (rodentia, artiodactyla, and primates). The average pattern of the 49 genes supports the prediction of the nearly neutral theory, with some notable exceptions. The nearly neutral theory also predicts that the variance of the evolutionary rate is larger than the value predicted by the completely neutral theory. This prediction is tested by examining the dispersion index (ratio of the variance to the mean), which is positively correlated with the average substitution number. After weighting by the lineage effects, this correlation almost disappears for nonsynonymous substitutions, but not quite so for synonymous substitutions. After weighting, the dispersion indices of both synonymous and nonsynonymous substitutions still exceed values expected under the simple Poisson process. The results indicate that both the systematic bias in evolutionary rate among the lineages and the episodic type of rate variation are contributing to the large variance. The former is more significant to synonymous substitutions than to nonsynonymous substitutions. Isochore evolution may be similar to synonymous substitutions. The rate and pattern found here are consistent with the nearly neutral theory, such that the relative contributions of drift and selection differ between the two types of substitutions. The results are also consistent with Gillespie's episodic selection theory.},
	language = {eng},
	number = {1},
	journal = {J. Mol. Evol.},
	author = {Ohta, T.},
	month = jan,
	year = {1995},
	pmid = {7714912},
	keywords = {Animals, Biological Evolution, Mammals, Models, Theoretical},
	pages = {56--63}
}

@article{abagyan_icm_1994,
	title = {{ICM} — a new method for protein modeling and design. {Applications} to docking and structure prediction from the distorted native conformation},
	volume = {15},
	journal = {J. Comput. Chem.},
	author = {Abagyan, R. and Totrov, M. and Kuznetsov, D.N.},
	year = {1994},
	pages = {488--506}
}

@article{nordling_medium-chain_2002,
	title = {Medium-chain dehydrogenases/reductases ({MDR}). {Family} characterizations including genome comparisons and active site modeling},
	volume = {269},
	issn = {0014-2956},
	abstract = {Completed eukaryotic genomes were screened for medium-chain dehydrogenases/reductases (MDR). In the human genome, 23 MDR forms were found, a number that probably will increase, because the genome is not yet fully interpreted. Partial sequences already indicate that at least three further members exist. Within the MDR superfamily, at least eight families were distinguished. Three families are formed by dimeric alcohol dehydrogenases (ADH; originally detected in animals/plants), cinnamyl alcohol dehydrogenases (originally detected in plants) and tetrameric alcohol dehydrogenases (originally detected in yeast). Three further families are centred around forms initially detected as mitochondrial respiratory function proteins, acetyl-CoA reductases of fatty acid synthases, and leukotriene B4 dehydrogenases. The two remaining families with polyol dehydrogenases (originally detected as sorbitol dehydrogenase) and quinone reductases (originally detected as zeta-crystallin) are also distinct but with variable sequences. The most abundant families in the human genome are the dimeric ADH forms and the quinone oxidoreductases. The eukaryotic patterns are different from those of Escherichia coli. The different families were further evaluated by molecular modelling of their active sites as to geometry, hydrophobicity and volume of substrate-binding pockets. Finally, sequence patterns were derived that are diagnostic for the different families and can be used in genome annotations.},
	language = {eng},
	number = {17},
	journal = {Eur J Biochem},
	author = {Nordling, Erik and Jörnvall, Hans and Persson, Bengt},
	month = sep,
	year = {2002},
	pmid = {12199705},
	keywords = {Amino Acid Motifs, Binding Sites, Crystallins, Evolution, Molecular, Genome, Human, Humans, Models, Molecular, Oxidoreductases, Phylogeny, Quinone Reductases},
	pages = {4267--4276}
}

@article{jain_infrastructure_2009,
	title = {Infrastructure for the life sciences: design and implementation of the {UniProt} website},
	volume = {10},
	journal = {BMC Bioinformatics},
	author = {Jain, E and Bairoch, A and Duvaud, S and Phan, I and Redaschi, N and Suzek, B E and Martin, M J and McGarvey, P and Gasteiger, E},
	year = {2009},
	pages = {136}
}

@article{cardozo_homology_1995,
	title = {Homology modeling by the {ICM} method},
	volume = {23},
	issn = {0887-3585},
	doi = {10.1002/prot.340230314},
	abstract = {Five models have been built by the ICM method for the Comparative Modeling section of the Meeting on the Critical Assessment of Techniques for Protein Structure Prediction. The targets have homologous proteins with known three-dimensional structure with sequence identity ranging from 25 to 77\%. After alignment of the target sequence with the related three-dimensional structure, the modeling procedure consists of two subproblems: side-chain prediction and loop prediction. The ICM method approaches these problems with the following steps: (1) a starting model is created based on the homologous structure with the conserved portion fixed and the nonconserved portion having standard covalent geometry and free torsion angles; (2) the Biased Probability Monte Carlo (BPMC) procedure is applied to search the subspaces of either all the nonconservative side-chain torsion angles or torsion angles in a loop backbone and surrounding side chains. A special algorithm was designed to generate low-energy loop deformations. The BPMC procedure globally optimizes the energy function consisting of ECEPP/3 and solvation energy terms. Comparison of the predictions with the NMR or crystallographic solutions reveals a high proportion of correctly predicted side chains. The loops were not correctly predicted because imprinted distortions of the backbone increased the energy of the near-native conformation and thus made the solution unrecognizable. Interestingly, the energy terms were found to be reliable and the sampling of conformational space sufficient. The implications of this finding for the strategies of future comparative modeling are discussed.},
	language = {eng},
	number = {3},
	journal = {Proteins},
	author = {Cardozo, T. and Totrov, M. and Abagyan, R.},
	month = nov,
	year = {1995},
	pmid = {8710833},
	keywords = {Antibodies, Anti-Idiotypic, Bacterial Proteins, Computer Graphics, Computer Simulation, Cytochrome P-450 Enzyme System, Databases, Factual, Helix-Turn-Helix Motifs, Mixed Function Oxygenases, Models, Molecular, Monte Carlo Method, Muramidase, Nucleoside-Diphosphate Kinase, Phosphoenolpyruvate Sugar Phosphotransferase System, Protein Conformation, Proteins, Protein Structure, Secondary, Protein Structure, Tertiary, Receptors, Retinoic Acid, Sequence Alignment, Sequence Homology, Amino Acid},
	pages = {403--414}
}

@article{eklund_structural_1976,
	title = {Structural comparisons of mammalian, yeast and bacillar alcohol dehydrogenases},
	volume = {102},
	issn = {0022-2836},
	language = {eng},
	number = {1},
	journal = {J. Mol. Biol.},
	author = {Eklund, H. and Brändén, C. I. and Jörnvall, H.},
	month = mar,
	year = {1976},
	pmid = {775100},
	keywords = {Alcohol Oxidoreductases, Amino Acids, Amino Acid Sequence, Binding Sites, Biological Evolution, Geobacillus stearothermophilus, Liver, Models, Molecular, Protein Binding, Protein Conformation, Saccharomyces cerevisiae, Species Specificity},
	pages = {61--73}
}

@article{pronk_gromacs_2013,
	title = {{GROMACS} 4.5: {A} high-throughput and highly parallel open source molecular simulation toolkit},
	volume = {29},
	issn = {1367-4811},
	shorttitle = {{GROMACS} 4.5},
	doi = {10.1093/bioinformatics/btt055},
	abstract = {MOTIVATION: Molecular simulation has historically been a low-throughput technique, but faster computers and increasing amounts of genomic and structural data are changing this by enabling large-scale automated simulation of, for instance, many conformers or mutants of biomolecules with or without a range of ligands. At the same time, advances in performance and scaling now make it possible to model complex biomolecular interaction and function in a manner directly testable by experiment. These applications share a need for fast and efficient software that can be deployed on massive scale in clusters, web servers, distributed computing or cloud resources.
RESULTS: Here, we present a range of new simulation algorithms and features developed during the past 4 years, leading up to the GROMACS 4.5 software package. The software now automatically handles wide classes of biomolecules, such as proteins, nucleic acids and lipids, and comes with all commonly used force fields for these molecules built-in. GROMACS supports several implicit solvent models, as well as new free-energy algorithms, and the software now uses multithreading for efficient parallelization even on low-end systems, including windows-based workstations. Together with hand-tuned assembly kernels and state-of-the-art parallelization, this provides extremely high performance and cost efficiency for high-throughput as well as massively parallel simulations.
AVAILABILITY: GROMACS is an open source and free software available from http://www.gromacs.org.
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.},
	language = {eng},
	number = {7},
	journal = {Bioinformatics},
	author = {Pronk, Sander and Páll, Szilárd and Schulz, Roland and Larsson, Per and Bjelkmar, Pär and Apostolov, Rossen and Shirts, Michael R and Smith, Jeremy C and Kasson, Peter M and van der Spoel, David and Hess, Berk and Lindahl, Erik},
	month = apr,
	year = {2013},
	pmid = {23407358},
	pages = {845--854}
}

@article{jornvall_short-chain_1995,
	title = {Short-chain dehydrogenases/reductases ({SDR})},
	volume = {34},
	issn = {0006-2960},
	abstract = {Short-chain dehydrogenases/reductases (SDR) constitute a large protein family. Presently, at least 57 characterized, highly different enzymes belong to this family and typically exhibit residue identities only at the 15-30\% level, indicating early duplicatory origins and extensive divergence. In addition, another family of 22 enzymes with extended protein chains exhibits part-chain SDR relationships and represents enzymes of no less than three EC classes. Furthermore, subforms and species variants are known of both families. In the combined SDR superfamily, only one residue is strictly conserved and ascribed a crucial enzymatic function (Tyr 151 in the numbering system of human NAD(+)-linked prostaglandin dehydrogenase). Such a function for this Tyr residue in SDR enzymes in general is supported also by chemical modifications, site-directed mutagenesis, and an active site position in those tertiary structures that have been characterized. A lysine residue four residues downstream is also largely conserved. A model for catalysis is available on the basis of these two residues. Binding of the coenzyme, NAD(H) or NADP(H), is in the N-terminal part of the molecules, where a common GlyXXXGlyXGly pattern occurs. Two SDR enzymes established by X-ray crystallography show a one-domain subunit with seven to eight beta-strands. Conformational patterns are highly similar, except for variations in the C-terminal parts. Additional structures occur in the family with extended chains. Some of the SDR molecules are known under more than one name, and one of the enzymes has been shown to be susceptible to native, chemical modification, producing reduced Schiff base adducts with pyruvate and other metabolic keto derivatives. Most SDR enzymes are dimers and tetramers. In those analyzed, the area of major subunit contacts involves two long alpha-helices (alpha E, alpha F) in similar and apparently strong subunit interactions. Future possibilities include verification of the proposed reaction mechanism and tracing of additional relationships, perhaps also with other protein families. Short-chain dehydrogenases illustrate the value of comparisons and diversified research in generating unexpected discoveries.},
	language = {eng},
	number = {18},
	journal = {Biochemistry},
	author = {Jörnvall, H. and Persson, B. and Krook, M. and Atrian, S. and Gonzàlez-Duarte, R. and Jeffery, J. and Ghosh, D.},
	month = may,
	year = {1995},
	pmid = {7742302},
	keywords = {Amino Acid Sequence, Animals, Models, Molecular, Molecular Sequence Data, Mutagenesis, Site-Directed, Oxidoreductases, Phylogeny, Protein Conformation, Sequence Alignment},
	pages = {6003--6013}
}

@article{bussi_canonical_2007,
	title = {Canonical sampling through velocity rescaling},
	volume = {126},
	journal = {J. Chem. Phys.},
	author = {Bussi, G and Donadio, D and Parrinello, M},
	year = {2007},
	pages = {014101}
}

@article{leaver-fay_rosetta3:_2011,
	title = {{ROSETTA}3: an object-oriented software suite for the simulation and design of macromolecules},
	volume = {487},
	journal = {Methods Enzymol},
	author = {Leaver-Fay, A. and Tyka, M. and Lewis, S.M. and Lange, O.F. and Thompson, J. and Jacak, R. and Kaufman, K. and Renfrew, P.D. and Smith, C.A. and Sheffler, W. and others},
	year = {2011},
	pages = {545--574}
}

@misc{noauthor_adh6_nodate,
	type = {Database},
	title = {{ADH}6 in {PeptideAtlas}},
	urldate = {2014-11-06},
	journal = {PeptideAtlas}
}

@article{kim_pubchem_2016,
	title = {{PubChem} {Substance} and {Compound} databases},
	volume = {44},
	issn = {0305-1048},
	doi = {10.1093/nar/gkv951},
	abstract = {PubChem (https://pubchem.ncbi.nlm.nih.gov) is a public repository for information on chemical substances and their biological activities, launched in 2004 as a component of the Molecular Libraries Roadmap Initiatives of the US National Institutes of Health (NIH). For the past 11 years, PubChem has grown to a sizable system, serving as a chemical information resource for the scientific research community. PubChem consists of three inter-linked databases, Substance, Compound and BioAssay. The Substance database contains chemical information deposited by individual data contributors to PubChem, and the Compound database stores unique chemical structures extracted from the Substance database. Biological activity data of chemical substances tested in assay experiments are contained in the BioAssay database. This paper provides an overview of the PubChem Substance and Compound databases, including data sources and contents, data organization, data submission using PubChem Upload, chemical structure standardization, web-based interfaces for textual and non-textual searches, and programmatic access. It also gives a brief description of PubChem3D, a resource derived from theoretical three-dimensional structures of compounds in PubChem, as well as PubChemRDF, Resource Description Framework (RDF)-formatted PubChem data for data sharing, analysis and integration with information contained in other databases.},
	number = {Database issue},
	urldate = {2017-03-30},
	journal = {Nucleic Acids Res},
	author = {Kim, Sunghwan and Thiessen, Paul A. and Bolton, Evan E. and Chen, Jie and Fu, Gang and Gindulyte, Asta and Han, Lianyi and He, Jane and He, Siqian and Shoemaker, Benjamin A. and Wang, Jiyao and Yu, Bo and Zhang, Jian and Bryant, Stephen H.},
	month = jan,
	year = {2016},
	pmid = {26400175},
	pmcid = {PMC4702940},
	pages = {D1202--D1213},
	file = {PubMed Central Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/ZZ296VBF/Kim et al. - 2016 - PubChem Substance and Compound databases.pdf:application/pdf}
}

@article{carlsson_investigation_2009,
	title = {Investigation and prediction of the severity of p53 mutants using parameters from structural calculations.},
	volume = {276},
	doi = {10.1111/j.1742-4658.2009.07124.x},
	abstract = {A method has been developed to predict the effects of mutations in the p53 cancer suppressor gene. The new method uses novel parameters combined with previously established parameters. The most important parameter is the stability measure of the mutated structure calculated using molecular modelling. For each mutant, a severity score is reported, which can be used for classification into deleterious and nondeleterious. Both structural features and sequence properties are taken into account. The method has a prediction accuracy of 77\% on all mutants and 88\% on breast cancer mutations affecting WAF1 promoter binding. When compared with earlier methods, using the same dataset, our method clearly performs better. As a result of the severity score calculated for every mutant, valuable knowledge can be gained regarding p53, a protein that is believed to be involved in over 50\% of all human cancers.},
	number = {15},
	journal = {FEBS J.},
	author = {Carlsson, Jonas and Soussi, Thierry and Persson, Bengt},
	month = aug,
	year = {2009},
	pages = {4142--55}
}

@article{do_probcons:_2005,
	title = {{ProbCons}: {Probabilistic} consistency-based multiple sequence alignment},
	volume = {15},
	issn = {1088-9051},
	shorttitle = {{ProbCons}},
	doi = {10.1101/gr.2821705},
	abstract = {To study gene evolution across a wide range of organisms, biologists need accurate tools for multiple sequence alignment of protein families. Obtaining accurate alignments, however, is a difficult computational problem because of not only the high computational cost but also the lack of proper objective functions for measuring alignment quality. In this paper, we introduce probabilistic consistency, a novel scoring function for multiple sequence comparisons. We present ProbCons, a practical tool for progressive protein multiple sequence alignment based on probabilistic consistency, and evaluate its performance on several standard alignment benchmark data sets. On the BAliBASE, SABmark, and PREFAB benchmark alignment databases, ProbCons achieves statistically significant improvement over other leading methods while maintaining practical speed. ProbCons is publicly available as a Web resource.},
	language = {eng},
	number = {2},
	journal = {Genome Res.},
	author = {Do, Chuong B. and Mahabhashyam, Mahathi S. P. and Brudno, Michael and Batzoglou, Serafim},
	month = feb,
	year = {2005},
	pmid = {15687296},
	pmcid = {PMC546535},
	keywords = {Algorithms, Amino Acid Sequence, Benchmarking, Computational Biology, Databases, Protein, Genetic Variation, Molecular Sequence Data, Sequence Alignment, Software, Software Validation},
	pages = {330--340}
}

@article{kiefer_swiss-model_2009,
	title = {The {SWISS}-{MODEL} {Repository} and associated resources},
	volume = {37},
	issn = {1362-4962},
	doi = {10.1093/nar/gkn750},
	abstract = {SWISS-MODEL Repository (http://swissmodel.expasy.org/repository/) is a database of 3D protein structure models generated by the SWISS-MODEL homology-modelling pipeline. The aim of the SWISS-MODEL Repository is to provide access to an up-to-date collection of annotated 3D protein models generated by automated homology modelling for all sequences in Swiss-Prot and for relevant models organisms. Regular updates ensure that target coverage is complete, that models are built using the most recent sequence and template structure databases, and that improvements in the underlying modelling pipeline are fully utilised. As of September 2008, the database contains 3.4 million entries for 2.7 million different protein sequences from the UniProt database. SWISS-MODEL Repository allows the users to assess the quality of the models in the database, search for alternative template structures, and to build models interactively via SWISS-MODEL Workspace (http://swissmodel.expasy.org/workspace/). Annotation of models with functional information and cross-linking with other databases such as the Protein Model Portal (http://www.proteinmodelportal.org) of the PSI Structural Genomics Knowledge Base facilitates the navigation between protein sequence and structure resources.},
	language = {eng},
	number = {Database issue},
	journal = {Nucleic Acids Res.},
	author = {Kiefer, Florian and Arnold, Konstantin and Künzli, Michael and Bordoli, Lorenza and Schwede, Torsten},
	month = jan,
	year = {2009},
	pmid = {18931379},
	pmcid = {PMC2686475},
	keywords = {Animals, Computer Graphics, Databases, Protein, Humans, Models, Molecular, Structural Homology, Protein, User-Computer Interface},
	pages = {D387--392}
}

@article{uhlen_towards_2010,
	title = {Towards a knowledge-based {Human} {Protein} {Atlas}},
	volume = {28},
	issn = {1546-1696},
	doi = {10.1038/nbt1210-1248},
	language = {eng},
	number = {12},
	journal = {Nat. Biotechnol.},
	author = {Uhlen, Mathias and Oksvold, Per and Fagerberg, Linn and Lundberg, Emma and Jonasson, Kalle and Forsberg, Mattias and Zwahlen, Martin and Kampf, Caroline and Wester, Kenneth and Hober, Sophia and Wernerus, Henrik and Björling, Lisa and Ponten, Fredrik},
	month = dec,
	year = {2010},
	pmid = {21139605},
	keywords = {Database Management Systems, Databases, Protein, Humans, Organ Specificity, Proteins, Software, User-Computer Interface},
	pages = {1248--1250}
}

@article{the_uniprot_consortium_universal_2010,
	title = {The {Universal} {Protein} {Resource} ({UniProt}) in 2010},
	journal = {Nucleic Acids Res.},
	author = {{The UniProt Consortium}},
	year = {2010},
	pages = {D142--D148}
}

@article{hoog_mammalian_2001,
	title = {Mammalian alcohol dehydrogenase of higher classes: analyses of human {ADH}5 and rat {ADH}6},
	volume = {130–132},
	issn = {0009-2797},
	shorttitle = {Mammalian alcohol dehydrogenase of higher classes},
	doi = {10.1016/S0009-2797(00)00264-7},
	abstract = {Alcohol dehydrogenases (ADH) of classes V and VI, ADH5 and ADH6, have been defined in man and rodents, respectively. Sequence data have been obtained at cDNA and genomic levels, but limited data are available for functionality and substrate repertoire. The low positional identity (65\%) between the two ADHs, place them into separate classes. We have shown that the ADH5 gene yields two differently processed mRNAs and harbors a gene organization identical to other mammalian ADHs. This is probably due to an alternative splicing in the eighth intron that results in a shorter message missing the ninth exon or a normal message with the expected number of codons. The isolated rat ADH6 cDNA was found to be fused to ADH2 at the 5′-end. The resulting main open reading frame translates into an N-terminally extended polypeptide. In vitro translation results in a polypeptide of about 42 kDa and further, protein was possible to express in COS cells as a fusion product with Green Fluorescent Protein. Both ADH5 and ADH6 show genes and gene products that are processed comparably to other mammalian ADHs and the deduced amino acid sequences indicate a lack of ethanol dehydrogenase activity that probably explains why no corresponding proteins have been isolated. The functionality of these ADHs is therefore still an enigma.},
	urldate = {2013-08-26},
	journal = {Chemico-Biological Interactions},
	author = {Höög, Jan-Olov and Brandt, Margareta and Hedberg, Jesper J. and Stromberg, Patrik},
	month = jan,
	year = {2001},
	keywords = {Alcohol Dehydrogenase, alternative splicing, Classes, Protein expression},
	pages = {395--404},
	file = {ScienceDirect Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/3CX3A3GG/Höög et al. - 2001 - Mammalian alcohol dehydrogenase of higher classes.pdf:application/pdf;ScienceDirect Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/TAHXDEMS/S0009279700002647.html:text/html}
}

@article{hellgren_alcohol_2007,
	title = {Alcohol dehydrogenase 2 is a major hepatic enzyme for human retinol metabolism},
	volume = {64},
	issn = {1420-682X},
	doi = {10.1007/s00018-007-6449-8},
	abstract = {The metabolism of all-trans- and 9-cis-retinol/ retinaldehyde has been investigated with focus on the activities of human, mouse and rat alcohol dehydrogenase 2 (ADH2), an intriguing enzyme with apparently different functions in human and rodents. Kinetic constants were determined with an HPLC method and a structural approach was implemented by in silico substrate dockings. For human ADH2, the determined K(m) values ranged from 0.05 to 0.3 microM and k(cat) values from 2.3 to 17.6 min(-1), while the catalytic efficiency for 9-cis-retinol showed the highest value for any substrate. In contrast, poor activities were detected for the rodent enzymes. A mouse ADH2 mutant (ADH2Pro47His) was studied that resembles the human ADH2 setup. This mutation increased the retinoid activity up to 100-fold. The K(m) values of human ADH2 are the lowest among all known human retinol dehydrogenases, which clearly support a role in hepatic retinol oxidation at physiological concentrations.},
	language = {eng},
	number = {4},
	journal = {Cell. Mol. Life Sci.},
	author = {Hellgren, M. and Strömberg, P. and Gallego, O. and Martras, S. and Farrés, J. and Persson, B. and Parés, X. and Höög, J.-O.},
	month = feb,
	year = {2007},
	pmid = {17279314},
	keywords = {Alcohol Dehydrogenase, Amino Acid Sequence, Animals, Binding Sites, Humans, Kinetics, Liver, Mice, Models, Molecular, Molecular Sequence Data, Protein Structure, Secondary, Rats, Sequence Alignment, Vitamin A},
	pages = {498--505}
}

@article{schapira_rational_2000,
	title = {Rational discovery of novel nuclear hormone receptor antagonists},
	volume = {97},
	journal = {Proc. Natl. Acad. Sci. U. S. A.},
	author = {Schapira, M and Raaka, B M and Samuels, H H and Abagyan, R},
	year = {2000},
	pages = {1008--1013}
}

@misc{noauthor_adh6_nodate-1,
	type = {Database},
	title = {{ADH}6 in the {Human} {Protein} {Atlas}},
	urldate = {2014-12-11}
}

@article{han_developing_2008,
	title = {Developing and validating predictive decision tree models from mining chemical structural fingerprints and high-throughput screening data in {PubChem}},
	volume = {9},
	journal = {BMC Bioinformatics},
	author = {Han, L and Wang, Y and Bryant, S H},
	year = {2008},
	pages = {401}
}

@article{svensson_crystal_2000,
	title = {Crystal structures of mouse class {II} alcohol dehydrogenase reveal determinants of substrate specificity and catalytic efficiency},
	volume = {302},
	issn = {0022-2836},
	doi = {10.1006/jmbi.2000.4039},
	abstract = {The structure of mouse class II alcohol dehydrogenase (ADH2) has been determined in a binary complex with the coenzyme NADH and in a ternary complex with both NADH and the inhibitor N-cyclohexylformamide to 2.2 A and 2.1 A resolution, respectively. The ADH2 dimer is asymmetric in the crystal with different orientations of the catalytic domains relative to the coenzyme-binding domains in the two subunits, resulting in a slightly different closure of the active-site cleft. Both conformations are about half way between the open apo structure and the closed holo structure of horse ADH1, thus resembling that of ADH3. The semi-open conformation and structural differences around the active-site cleft contribute to a substantially different substrate-binding pocket architecture as compared to other classes of alcohol dehydrogenase, and provide the structural basis for recognition and selectivity of alcohols and quinones. The active-site cleft is more voluminous than that of ADH1 but not as open and funnel-shaped as that of ADH3. The loop with residues 296-301 from the coenzyme-binding domain is short, thus opening up the pocket towards the coenzyme. On the opposite side, the loop with residues 114-121 stretches out over the inter-domain cleft. A cavity is formed below this loop and adds an appendix to the substrate-binding pocket. Asp301 is positioned at the entrance of the pocket and may control the binding of omega-hydroxy fatty acids, which act as inhibitors rather than substrates. Mouse ADH2 is known as an inefficient ADH with a slow hydrogen-transfer step. By replacing Pro47 with His, the alcohol dehydrogenase activity is restored. Here, the structure of this P47H mutant was determined in complex with NADH to 2.5 A resolution. His47 is suitably positioned to act as a catalytic base in the deprotonation of the substrate. Moreover, in the more closed subunit, the coenzyme is allowed a position closer to the catalytic zinc. This is consistent with hydrogen transfer from an alcoholate intermediate where the Pro/His replacement focuses on the function of the enzyme.},
	language = {eng},
	number = {2},
	journal = {J. Mol. Biol.},
	author = {Svensson, S. and Höög, J-O and Schneider, G. and Sandalova, T.},
	month = sep,
	year = {2000},
	pmid = {10970744},
	keywords = {Alcohol Dehydrogenase, Amino Acid Substitution, Animals, Apoenzymes, Binding Sites, Catalysis, Crystallography, X-Ray, Dimerization, Formamides, Holoenzymes, Hydrogen, Hydrogen Bonding, Lauric Acids, Mice, Models, Molecular, Mutation, NAD, Protein Structure, Secondary, Protein Structure, Tertiary, Static Electricity, Substrate Specificity},
	pages = {441--453}
}

@article{rao_comparison_1973,
	title = {Comparison of super-secondary structures in proteins},
	volume = {76},
	issn = {0022-2836},
	language = {eng},
	number = {2},
	journal = {J. Mol. Biol.},
	author = {Rao, S. T. and Rossmann, M. G.},
	month = may,
	year = {1973},
	pmid = {4737475},
	keywords = {Amino Acids, Amino Acid Sequence, Animals, Apoproteins, Chemical Phenomena, Chemistry, Flavoproteins, L-Lactate Dehydrogenase, Malate Dehydrogenase, Mathematics, Models, Structural, Protein Conformation, Sharks, Solubility, Subtilisins},
	pages = {241--256}
}

@article{finn_pfam:_2014,
	title = {Pfam: {The} protein families database},
	volume = {42},
	issn = {0305-1048, 1362-4962},
	shorttitle = {Pfam},
	doi = {10.1093/nar/gkt1223},
	abstract = {Pfam, available via servers in the UK (http://pfam.sanger.ac.uk/) and the USA (http://pfam.janelia.org/), is a widely used database of protein families, containing 14 831 manually curated entries in the current release, version 27.0. Since the last update article 2 years ago, we have generated 1182 new families and maintained sequence coverage of the UniProt Knowledgebase (UniProtKB) at nearly 80\%, despite a 50\% increase in the size of the underlying sequence database. Since our 2012 article describing Pfam, we have also undertaken a comprehensive review of the features that are provided by Pfam over and above the basic family data. For each feature, we determined the relevance, computational burden, usage statistics and the functionality of the feature in a website context. As a consequence of this review, we have removed some features, enhanced others and developed new ones to meet the changing demands of computational biology. Here, we describe the changes to Pfam content. Notably, we now provide family alignments based on four different representative proteome sequence data sets and a new interactive DNA search interface. We also discuss the mapping between Pfam and known 3D structures.},
	language = {en},
	number = {D1},
	urldate = {2015-04-28},
	journal = {Nucl. Acids Res.},
	author = {Finn, Robert D. and Bateman, Alex and Clements, Jody and Coggill, Penelope and Eberhardt, Ruth Y. and Eddy, Sean R. and Heger, Andreas and Hetherington, Kirstie and Holm, Liisa and Mistry, Jaina and Sonnhammer, Erik L. L. and Tate, John and Punta, Marco},
	month = jan,
	year = {2014},
	pmid = {24288371},
	pages = {D222--D230},
	file = {Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/VMA247AT/Finn et al. - 2014 - Pfam the protein families database.pdf:application/pdf;Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/XD2RMUWX/Finn et al. - 2014 - Pfam the protein families database.html:text/html}
}

@article{hess_gromacs_2008,
	title = {{GROMACS} 4: {Algorithms} for highly efficient, load-balanced, and scalable molecular simulation},
	volume = {4},
	number = {3},
	journal = {J. Chem. Theory Comput.},
	author = {Hess, Berk and Kutzner, Carsten and Van der Spoel, David and Lindahl, Erik},
	year = {2008},
	pages = {435--47}
}

@article{scott_gromos_1999,
	title = {The {GROMOS} {Biomolecular} {Simulation} {Program} {Package}},
	volume = {103},
	number = {19},
	journal = {J Phys Chem A},
	author = {Scott, W R P and Hünenberger, P H and Tironi, I G and Mark, A E and Billeter, S R and Fennen, J and Torda, A E and Huber, T andKrüger P and van Gunsteren, Wilfred F},
	year = {1999},
	pages = {3596--3607}
}

@article{finn_interpro_2017,
	title = {{InterPro} in 2017—beyond protein family and domain annotations},
	volume = {45},
	issn = {0305-1048},
	doi = {10.1093/nar/gkw1107},
	number = {D1},
	urldate = {2017-03-24},
	journal = {Nucleic Acids Res},
	author = {Finn, Robert D. and Attwood, Teresa K. and Babbitt, Patricia C. and Bateman, Alex and Bork, Peer and Bridge, Alan J. and Chang, Hsin-Yu and Dosztányi, Zsuzsanna and El-Gebali, Sara and Fraser, Matthew and Gough, Julian and Haft, David and Holliday, Gemma L. and Huang, Hongzhan and Huang, Xiaosong and Letunic, Ivica and Lopez, Rodrigo and Lu, Shennan and Marchler-Bauer, Aron and Mi, Huaiyu and Mistry, Jaina and Natale, Darren A. and Necci, Marco and Nuka, Gift and Orengo, Christine A. and Park, Youngmi and Pesseat, Sebastien and Piovesan, Damiano and Potter, Simon C. and Rawlings, Neil D. and Redaschi, Nicole and Richardson, Lorna and Rivoire, Catherine and Sangrador-Vegas, Amaia and Sigrist, Christian and Sillitoe, Ian and Smithers, Ben and Squizzato, Silvano and Sutton, Granger and Thanki, Narmada and Thomas, Paul D. and Tosatto, Silvio C. E. and Wu, Cathy H. and Xenarios, Ioannis and Yeh, Lai-Su and Young, Siew-Yit and Mitchell, Alex L.},
	month = jan,
	year = {2017},
	pages = {D190--D199},
	file = {Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/A22USMEE/Finn et al. - 2017 - InterPro in 2017—beyond protein family and domain .pdf:application/pdf;Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/5EJDQUN8/InterPro-in-2017-beyond-protein-family-and-domain.html:text/html}
}

@article{bergman_zinc_2008,
	title = {Zinc binding to peptide analogs of the structural zinc site in alcohol dehydrogenase: {Implications} for an entatic state},
	volume = {65},
	journal = {Cell. Mol. Life. Sci.},
	author = {Bergman, Tomas and Zhang, K and Palmberg, C and Jörnvall, H and Auld, D. S.},
	year = {2008},
	pages = {4019--4027}
}

@article{lindahl_gromacs_2001,
	title = {{GROMACS} 3.0: {A} package for molecular simulation and trajectory analysis},
	volume = {7},
	journal = {J. Mol. Mod.},
	author = {Lindahl, E and Hess, B and van der Spoel, D},
	year = {2001},
	pages = {306--317}
}

@article{ginalski_orfeus:_2003,
	title = {{ORFeus}: {Detection} of distant homology using sequence profiles and predicted secondary structure},
	volume = {31},
	number = {13},
	journal = {Nucleic Acids Res.},
	author = {Ginalski, K and Pas, J and Wyrwicz, LS and von Grotthuss, M and Bujnicki, JM and Rychlewski, L},
	year = {2003},
	pages = {3804--3807}
}

@article{persson_medium-_2008,
	title = {Medium- and short-chain dehydrogenase/reductase gene and protein families: the {MDR} superfamily},
	volume = {65},
	number = {24},
	journal = {Cell. Mol. Life. Sci.},
	author = {Persson, B and Hedlund, J and Jörnvall, H},
	year = {2008},
	pages = {3879--3894}
}

@article{ostberg_mammalian_2015,
	series = {17th {International} {Workshop} on the {Enzymology} and {Molecular} {Biology} of {Carbonyl} {Metabolism}},
	title = {The mammalian alcohol dehydrogenase genome shows several gene duplications and gene losses resulting in a large set of different enzymes including pseudoenzymes},
	volume = {234},
	issn = {0009-2797},
	doi = {10.1016/j.cbi.2014.11.020},
	abstract = {Mammalian alcohol dehydrogenase (ADH) is a protein family divided into six classes and the number of known family members is increasing rapidly. Several primate genomes are completely analyzed for the ADH region, where higher primates (human and hominoids) have seven genes of classes ADH1–ADH5. Within the group of non-hominoids apes there have been further duplications and species with more than the typical three isozymic forms for ADH1 are present. In contrast there are few completely analyzed ADH genomes in the non-primate group of mammals, where an additional class has been identified, ADH6, that has been lost during the evolution of primates. In this study 85 mammalian genomes with at least one ADH gene have been compiled. In total more than 500 ADH amino acid sequences were analyzed for patterns that distinguish the different classes.

For ADH1–ADH4 intensive investigations have been performed both at the functional and at structural levels. However, a corresponding functional protein to the ADH5 gene, which is found in most ADH genomes, has never been detected. The same is true for ADH6, which is only present in non-primates.

The entire mammalian ADH family shows a broad spectrum of gene duplications and gene losses where the numbers differ from six genes (most non-primate mammals) up to ten genes (vole). Included in these sets are examples of pseudogenes and pseudoenzymes.},
	urldate = {2015-04-24},
	journal = {Chem. Biol. Interact.},
	author = {Östberg, Linus J. and Persson, Bengt and Höög, Jan-Olov},
	month = jun,
	year = {2015},
	keywords = {Alcohol Dehydrogenase, Gene duplications, Phylogenetic tree, Protein sequences, Pseudoenzyme},
	pages = {80--84}
}

@article{voelz_molecular_2010,
	title = {Molecular {Simulation} of ab {Initio} {Protein} {Folding} for a {Millisecond} {Folder} {NTL}9(1−39)},
	volume = {132},
	issn = {0002-7863},
	doi = {10.1021/ja9090353},
	abstract = {To date, the slowest-folding proteins folded ab initio by all-atom molecular dynamics simulations have had folding times in the range of nanoseconds to microseconds. We report simulations of several folding trajectories of NTL9(1?39), a protein which has a folding time of ?1.5 ms. Distributed molecular dynamics simulations in implicit solvent on GPU processors were used to generate ensembles of trajectories out to ?40 ?s for several temperatures and starting states. At a temperature less than the melting point of the force field, we observe a small number of productive folding events, consistent with predictions from a model of parallel uncoupled two-state simulations. The posterior distribution of the folding rate predicted from the data agrees well with the experimental folding rate (?640/s). Markov State Models (MSMs) built from the data show a gap in the implied time scales indicative of two-state folding and heterogeneous pathways connecting diffuse mesoscopic substates. Structural analysis of the 14 out of 2000 macrostates transited by the top 10 folding pathways reveals that native-like pairing between strands 1 and 2 only occurs for macrostates with pfold {\textgreater} 0.5, suggesting ?12 hairpin formation may be rate-limiting. We believe that using simulation data such as these to seed adaptive resampling simulations will be a promising new method for achieving statistically converged descriptions of folding landscapes at longer time scales than ever before.},
	number = {5},
	urldate = {2014-02-17},
	journal = {J. Am. Chem. Soc.},
	author = {Voelz, Vincent A. and Bowman, Gregory R. and Beauchamp, Kyle and Pande, Vijay S.},
	month = feb,
	year = {2010},
	pages = {1526--1528},
	file = {ACS Full Text PDF w/ Links:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/TPJ5EWWS/Voelz et al. - 2010 - Molecular Simulation of ab Initio Protein Folding .pdf:application/pdf;ACS Full Text Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/GHZM9PV7/Voelz et al. - 2010 - Molecular Simulation of ab Initio Protein Folding .html:text/html}
}

@article{vallee_isozymes_1983,
	title = {Isozymes of human liver alcohol dehydrogenase},
	volume = {8},
	issn = {0160-3787},
	language = {eng},
	journal = {Isozymes Curr. Top. Biol. Med. Res.},
	author = {Vallee, B. L. and Bazzone, T. J.},
	year = {1983},
	pmid = {6354998},
	keywords = {Alcohol Dehydrogenase, Alcohol Oxidoreductases, Animals, Genetic Variation, Horses, Humans, Isoenzymes, Kinetics, Liver, Molecular Weight, Species Specificity, Substrate Specificity},
	pages = {219--244}
}

@article{landreh_subdivided_2014,
	title = {A subdivided molecular architecture with separate features and stepwise emergence among proinsulin {C}-peptides},
	volume = {450},
	issn = {1090-2104},
	doi = {10.1016/j.bbrc.2014.07.012},
	abstract = {The C-peptide of proinsulin exhibits multiple activities and several of the underlying molecular interactions are known. We recently showed that human C-peptide is sub-divided into a tripartite architecture and that the pattern, rather than the exact residue positions, is a characteristic feature. We have now analyzed 75 proinsulins, ranging from fish to human and find a limited co-evolution with insulin, but with many marked deviations. This suggests a complex relationship, in which not only insulin affects the evolution of C-peptide. A subdivided nature, however, is a characteristic feature among all C-peptides, with the N-terminal segment the one most conserved. This segment, ascribed chaperoning charge-interactions with insulin, suggests that the insulin interactions constitute a basic function, although largely shifting from Glu to Asp residues in C-peptides of lower life forms. A second conserved feature is a mid-segment with a high content of adjacent Pro and Gly residues, in mammalian C-peptides compatible with a turn structure, but with fewer and more distantly interspaced such residues in the non-mammalian forms, and even absent in several fish forms. However, this segment of coelacanth C-peptide possesses a unique Cys distribution, capable of forming a disulfide-stabilized turn. Finally, the C-terminal segment of mammalian C-peptides, ascribed a possible receptor-interacting function, is not really discernable in the sub-mammalian forms. Combined, these patterns suggest an evolutionary stepwise acquisition of the tripartite mammalian C-peptide molecule, with insulin-interaction being ancestral, various turn stabilizations apparently of intermediate emergence, and possible receptor-interaction the most recent addition.},
	language = {eng},
	number = {4},
	journal = {Biochem. Biophys. Res. Commun.},
	author = {Landreh, Michael and Östberg, Linus J. and Jörnvall, Hans},
	month = aug,
	year = {2014},
	pmid = {25017908},
	keywords = {Amino Acid Sequence, Animals, C-Peptide, Humans, Molecular Sequence Data, Protein Conformation, Sequence Homology, Amino Acid},
	pages = {1433--1438}
}

@article{fernandez-recio_optimal_2009,
	title = {Optimal docking area: a new method for predicting protein-protein interaction sites},
	volume = {58},
	journal = {Proteins},
	author = {Fernandez-Recio, J. and Totrov, M. and Skorodumov, C. and Abagyan, R.},
	year = {2009},
	pages = {134--143}
}

@article{wu_ab_2007,
	title = {Ab initio modeling of small proteins by iterative {TASSER} simulations},
	volume = {5},
	number = {1},
	journal = {BMC Biology},
	author = {Wu, Sitao and Skolnick, Jeffrey and Zhang, Yang},
	year = {2007},
	pages = {17}
}

@article{capella-gutierrez_trimal:_2009,
	title = {{trimAl}: {A} tool for automated alignment trimming in large-scale phylogenetic analyses.},
	volume = {25},
	author = {Capella-Gutierrez, Salvador and Silla-Martinez, Jose M and Gabaldon, Gabaldon},
	year = {2009},
	pages = {1972--1973}
}

@article{biasini_swiss-model:_2014,
	title = {{SWISS}-{MODEL}: modelling protein tertiary and quaternary structure using evolutionary information},
	volume = {42},
	issn = {0305-1048},
	shorttitle = {{SWISS}-{MODEL}},
	doi = {10.1093/nar/gku340},
	number = {W1},
	urldate = {2017-03-08},
	journal = {Nucleic Acids Res},
	author = {Biasini, Marco and Bienert, Stefan and Waterhouse, Andrew and Arnold, Konstantin and Studer, Gabriel and Schmidt, Tobias and Kiefer, Florian and Cassarino, Tiziano Gallo and Bertoni, Martino and Bordoli, Lorenza and Schwede, Torsten},
	month = jul,
	year = {2014},
	pages = {W252--W258},
	file = {Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/5RDDQNVD/Biasini et al. - 2014 - SWISS-MODEL modelling protein tertiary and quater.pdf:application/pdf;Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/QMVIPSIP/gku340.html:text/html}
}

@article{schwartz_structural_1976,
	title = {Structural analyses of mutant and wild-type alcohol dehydrogenases from drosophila melanogaster},
	volume = {68},
	issn = {0014-2956},
	abstract = {Four genetic variants of alcohol dehydrogenase from Drosophila melanogaster have been examined: wild-type F-enzyme (from the AdhF strain), the D-type mutant form (from the AdhD strain), which is catalytically active, and two proteins lacking enzymic activity (from the Adhn11 and Adhn5 strains). The proteins were compared by mapping of tryptic peptides. One pair of difference peptides was seen in the comparisons of the D and F-type enzymes. These peptides were purified and their sequences determined. The difference between the two proteins was shown to be an exchange at a single position of glycine in the F for glutamic acid in the D-type protein. This exchange is consistent with the greater acidity of alcohol dehydrogenase from the AdhD strain and can be produced by a single base mutation. The difference between the n11 and F-type proteins was not detected and is suggested to be in a large tryptic peptide. In addition to the difference peptides, other fragments from Drosophila alcohol dehydrogenase were isolated and analyzed. The sequences determined account for approximately 50\% of the amino acids in the protein and include regions around the two cysteine residues as well as possible terminal structures. All peptides analyzed were examined for structural identities with horse and yeast alcohol dehydrogenases. No clearly significant similarities were seen between the Drosophila enzyme and the other two proteins but low degrees of homology are possible. From the variations in cysteine-containing regions large differences appear to exist between the active sites of the insect enzyme and the other alcohol dehydrogenases.},
	language = {eng},
	number = {1},
	journal = {Eur. J. Biochem.},
	author = {Schwartz, M. F. and Jörnvall, H.},
	month = sep,
	year = {1976},
	pmid = {823018},
	keywords = {Alcohol Oxidoreductases, Amino Acids, Amino Acid Sequence, Animals, Carboxypeptidases, Drosophila melanogaster, Genetic Variation, Mutation, Peptide Fragments, Species Specificity, Trypsin},
	pages = {159--168}
}

@article{stromberg_enzymatic_2004,
	title = {Enzymatic mechanism of low-activity mouse alcohol dehydrogenase 2.},
	volume = {43},
	doi = {10.1021/bi0354482},
	abstract = {ADH2 is a member of one of the six classes of mammalian alcohol dehydrogenases, which catalyze the reversible oxidation of alcohols using NAD(+) as a cofactor. Within the ADH2 class, the rodent enzymes form a subgroup that exhibits low catalytic activity with all substrates that were examined, as compared to other groups, such as human ADH2. The low activity can be ascribed to the rigid nature of the proline residue at position 47 as the activity can be increased by approximately 100-fold by substituting Pro47 with either His (as found in human ADH2), Ala, or Gln. Mouse ADH2 follows an ordered bi-bi mechanism, and hydride transfer is rate-limiting for oxidation of benzyl alcohols catalyzed by the mutated and wild-type enzymes. Structural studies suggest that the mouse enzyme with His47 has a more closed active site, as compared to the enzyme with Pro47, and hydride transfer can be more efficient. Oxidation of benzyl alcohol catalyzed by all forms of the enzyme is strongly pH dependent, with pK values in the range of 8.1-9.3 for turnover numbers and catalytic efficiency. These pK values probably correspond to the ionization of the zinc-bound water or alcohol. The pK values are not lowered by the Pro47 to His substitution, suggesting that His47 does not act as a catalytic base in the deprotonation of the zinc ligand.},
	number = {5},
	journal = {Biochemistry},
	author = {Strömberg, Patrik and Svensson, Stefan and Berst, Kristine B and Plapp, Bryce V and Höög, Jan-Olov},
	month = feb,
	year = {2004},
	pages = {1323--8}
}

@article{zhang_cloning_2003,
	title = {Cloning and characterization of a novel splicing variant of the {ZADH}1 gene},
	volume = {103},
	issn = {1424-859X, 1424-8581},
	doi = {10.1159/000076293},
	number = {1-2},
	urldate = {2013-08-26},
	journal = {Cytogenetic and Genome Research},
	author = {Zhang, L. and Zhang, F. and Huo, K.},
	year = {2003},
	pages = {79--83},
	file = {Cytogenetic and Genome Research 2003, Vol. 103, No. 1-2 - Cloning and characterization of a novel splicing variant of the ZADH1 gene - FullText - Karger Publishers:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/2ERNGGDJ/76293.html:text/html}
}

@article{jornvall_horse_1970,
	title = {Horse liver alcohol dehydrogenase. {On} the primary structure of the ethanol-active isoenzyme},
	volume = {13},
	issn = {0014-2956},
	language = {eng},
	number = {3},
	journal = {Eur. J. Biochem.},
	author = {Jörnvall, H. and Harris, J. I.},
	month = apr,
	year = {1970},
	pmid = {5462776},
	keywords = {Alcohol Oxidoreductases, Amino Acids, Amino Acid Sequence, Animals, Autoradiography, Carbon Isotopes, Chromatography, DEAE-Cellulose, Chromatography, Gel, Cysteine, Ethanol, Guanidines, Horses, Iodoacetates, Isoenzymes, Liver, Methionine, Molecular Weight, Phenylalanine, Trypsin, Tryptophan},
	pages = {565--576}
}

@article{eklund_structure_1981,
	title = {Structure of a triclinic ternary complex of horse liver alcohol dehydrogenase at 2.9 {A} resolution},
	volume = {146},
	issn = {0022-2836},
	language = {eng},
	number = {4},
	journal = {J. Mol. Biol.},
	author = {Eklund, H. and Samma, J. P. and Wallén, L. and Brändén, C. I. and Akeson, A. and Jones, T. A.},
	month = mar,
	year = {1981},
	pmid = {7024556},
	keywords = {Alcohol Oxidoreductases, Animals, Apoenzymes, Binding Sites, Coenzymes, Crystallography, Dimethyl Sulfoxide, Horses, Liver, Macromolecular Substances, Models, Molecular, NAD, Protein Conformation},
	pages = {561--587}
}

@article{toribio_european_2017,
	title = {European {Nucleotide} {Archive} in 2016},
	volume = {45},
	issn = {1362-4962},
	doi = {10.1093/nar/gkw1106},
	abstract = {The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena) offers a rich platform for data sharing, publishing and archiving and a globally comprehensive data set for onward use by the scientific community. With a broad scope spanning raw sequencing reads, genome assemblies and functional annotation, the resource provides extensive data submission, search and download facilities across web and programmatic interfaces. Here, we outline ENA content and major access modalities, highlight major developments in 2016 and outline a number of examples of data reuse from ENA.},
	language = {eng},
	number = {D1},
	journal = {Nucleic Acids Res.},
	author = {Toribio, Ana Luisa and Alako, Blaise and Amid, Clara and Cerdeño-Tarrága, Ana and Clarke, Laura and Cleland, Iain and Fairley, Susan and Gibson, Richard and Goodgame, Neil and Ten Hoopen, Petra and Jayathilaka, Suran and Kay, Simon and Leinonen, Rasko and Liu, Xin and Martínez-Villacorta, Josué and Pakseresht, Nima and Rajan, Jeena and Reddy, Kethi and Rosello, Marc and Silvester, Nicole and Smirnov, Dmitriy and Vaughan, Daniel and Zalunin, Vadim and Cochrane, Guy},
	month = jan,
	year = {2017},
	pmid = {27899630},
	pmcid = {PMC5210577},
	pages = {D32--D36}
}

@article{landreh_transthyretin_2014,
	title = {Transthyretin microheterogeneity and molecular interactions: implications for amyloid formation},
	volume = {5},
	issn = {1868-503X},
	shorttitle = {Transthyretin microheterogeneity and molecular interactions},
	doi = {10.1515/bmc-2014-0006},
	abstract = {Aggregation of transthyretin (TTR), a plasma-binding protein for thyroxine and retinol-binding protein, is the cause of several amyloid diseases. Disease-associated mutations are well known, but wild-type TTR is, to a lesser extent, also amyloidogenic. Monomerization, not oligomer formation as in several other depository diseases, is the rate-limiting step in TTR aggregation, and stabilization of the natively tetrameric form can inhibit amyloid formation. Modifications on Cys10, as well as interactions with native ligands in plasma, were early found to influence the equilibrium between tetrameric and monomeric TTR by dissociating or stabilizing the tetramer. Following these discoveries, synthetic ligands for pharmacological prevention of TTR aggregation could be developed. In this article, we outline how the different types of TTR interactions and its microheterogeneity in plasma are related to its propensity to form amyloid fibrils. We conclude that plasma constituents and dietary components may act as natural TTR stabilizers whose mechanisms of action provide cues for the amelioration of TTR amyloid disease.},
	language = {eng},
	number = {3},
	journal = {Biomol Concepts},
	author = {Landreh, Michael and Östberg, Linus J. and Pettersson, Tom M. and Jörnvall, Hans},
	month = jun,
	year = {2014},
	pmid = {25372757},
	pages = {257--264}
}

@article{wierenga_interaction_1985,
	title = {Interaction of pyrophosphate moieties with .alpha.-helixes in dinucleotide-binding proteins},
	volume = {24},
	issn = {0006-2960},
	doi = {10.1021/bi00327a012},
	number = {6},
	urldate = {2017-03-06},
	journal = {Biochemistry},
	author = {Wierenga, Rik K. and De Maeyer, Marc C. H. and Hol, Wim G. J.},
	month = mar,
	year = {1985},
	pages = {1346--1357},
	file = {ACS Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/UNZBZ7ER/Wierenga et al. - 1985 - Interaction of pyrophosphate moieties with .alpha..pdf:application/pdf;ACS Full Text Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/69SQZMSN/bi00327a012.html:text/html}
}

@article{hoog_mammalian_2001-1,
	title = {Mammalian alcohol dehydrogenase - functional and structural implications},
	volume = {8},
	issn = {1021-7770},
	doi = {54015},
	abstract = {Mammalian alcohol dehydrogenase (ADH) constitutes a complex system with different forms and extensive multiplicity (ADH1-ADH6) that catalyze the oxidation and reduction of a wide variety of alcohols and aldehydes. The ADH1 enzymes, the classical liver forms, are involved in several metabolic pathways beside the oxidation of ethanol, e.g. norepinephrine, dopamine, serotonin and bile acid metabolism. This class is also able to further oxidize aldehydes into the corresponding carboxylic acids, i.e. dismutation. ADH2, can be divided into two subgroups, one group consisting of the human enzyme together with a rabbit form and another consisting of the rodent forms. The rodent enzymes almost lack ethanol-oxidizing capacity in contrast to the human form, indicating that rodents are poor model systems for human ethanol metabolism. ADH3 (identical to glutathione-dependent formaldehyde dehydrogenase) is clearly the ancestral ADH form and S-hydroxymethylglutathione is the main physiological substrate, but the enzyme can still oxidize ethanol at high concentrations. ADH4 is solely extrahepatically expressed and is probably involved in first pass metabolism of ethanol beside its role in retinol metabolism. The higher classes, ADH5 and ADH6, have been poorly investigated and their substrate repertoire is unknown. The entire ADH system can be seen as a general detoxifying system for alcohols and aldehydes without generating toxic radicals in contrast to the cytochrome P450 system.},
	language = {eng},
	number = {1},
	journal = {J. Biomed. Sci.},
	author = {Höög, J-O. and Hedberg, J. J. and Strömberg, P. and Svensson, S.},
	month = feb,
	year = {2001},
	pmid = {11173978},
	keywords = {Alcohol Dehydrogenase, Animals, Catalytic Domain, Cloning, Molecular, Ethanol, formaldehyde, Glutathione, Humans, Isoenzymes, Kinetics, Mammals, Oxidation-Reduction, Rats, Recombinant Proteins, Serotonin, Vitamin A},
	pages = {71--76}
}

@incollection{wu_bioinformatics:_2009,
	address = {New York},
	title = {Bioinformatics: {Tools} and {Applications}},
	publisher = {Springer Science},
	author = {Wu, Sitao and Zhang, Yang},
	editor = {Edwards, David and Stajich, Jason and Hansen, David},
	year = {2009},
	pages = {225--238}
}

@misc{the_international_human_genome_sequencing_consortium_international_2003,
	title = {International {Consortium} {Completes} {Human} {Genome} {Project}},
	url = {https://www.genome.gov/11006929/},
	urldate = {2017-05-02},
	author = {{The International Human Genome Sequencing Consortium}},
	month = apr,
	year = {2003}
}

@book{kukol_molecular_2008,
	address = {Totowa, NJ},
	title = {Molecular {Modeling} of {Proteins}},
	publisher = {Humana Press},
	editor = {Kukol, Andreas},
	year = {2008}
}

@article{marti-renom_comparative_2000,
	title = {Comparative protein structure modeling of genes and genomes},
	volume = {29},
	issn = {1056-8700},
	doi = {10.1146/annurev.biophys.29.1.291},
	abstract = {Comparative modeling predicts the three-dimensional structure of a given protein sequence (target) based primarily on its alignment to one or more proteins of known structure (templates). The prediction process consists of fold assignment, target-template alignment, model building, and model evaluation. The number of protein sequences that can be modeled and the accuracy of the predictions are increasing steadily because of the growth in the number of known protein structures and because of the improvements in the modeling software. Further advances are necessary in recognizing weak sequence-structure similarities, aligning sequences with structures, modeling of rigid body shifts, distortions, loops and side chains, as well as detecting errors in a model. Despite these problems, it is currently possible to model with useful accuracy significant parts of approximately one third of all known protein sequences. The use of individual comparative models in biology is already rewarding and increasingly widespread. A major new challenge for comparative modeling is the integration of it with the torrents of data from genome sequencing projects as well as from functional and structural genomics. In particular, there is a need to develop an automated, rapid, robust, sensitive, and accurate comparative modeling pipeline applicable to whole genomes. Such large-scale modeling is likely to encourage new kinds of applications for the many resulting models, based on their large number and completeness at the level of the family, organism, or functional network.},
	language = {eng},
	journal = {Annu Rev Biophys Biomol Struct},
	author = {Martí-Renom, M. A. and Stuart, A. C. and Fiser, A. and Sánchez, R. and Melo, F. and Sali, A.},
	year = {2000},
	pmid = {10940251},
	keywords = {Animals, Computer Simulation, Databases, Factual, Genome, Genomics, Humans, Models, Biological, Models, Genetic, Models, Molecular, Proteins},
	pages = {291--325}
}

@article{zhang_i-tasser_2008,
	title = {I-{TASSER} server for protein 3D structure prediction},
	volume = {9},
	number = {1},
	journal = {BMC Bioinformatics},
	author = {Zhang, Yang},
	year = {2008},
	pages = {40}
}

@article{abagyan_homology_1997,
	title = {Homology modeling with internal coordinate mechanics: deformation zone mapping and improvements of models via conformational search},
	volume = {Suppl 1},
	issn = {0887-3585},
	shorttitle = {Homology modeling with internal coordinate mechanics},
	abstract = {Five models by homology containing insertions and deletions and ranging from 33\% to 48\% sequence identity to the known homologue, and one high sequence identity (85\%) model were built for the CASP2 meeting. For all five low identity targets: (i) our starting models were improved by the Internal Coordinate Mechanics (ICM) energy optimization, (ii) the refined models were consistently better than those built with the automatic SWISS-MODEL program, and (iii) the refined models differed by less than 2\% from the best model submitted, as judged by the residue contact area difference (CAD) measure [Abagyan, R.A., Totrov, M.J. Mol. Biol. 268:678-685, 1997]. The CAD measure is proposed for ranking models built by homology instead of global root-mean-square deviation, which is frequently dominated by insignificant yet large contributions from incorrectly predicted fragments or side chains. We demonstrate that the precise identification of regions of local backbone deviation is an independent and crucial step in the homology modeling procedure after alignment, since aligned fragments can strongly deviate from the template at various distances from the alignment gap or even in the ungapped parts of the alignment. We show that a local alignment score can be used as an indicator of such local deviation. While four short loops of the meeting targets were predicted by database search, the best loop 1 target T0028, for which the correct database fragment was not found, was predicted by Internal Coordinate Mechanics global energy optimization at 1.2 A accuracy. A classification scheme for errors in homology modeling is proposed.},
	language = {eng},
	journal = {Proteins},
	author = {Abagyan, R. and Batalov, S. and Cardozo, T. and Totrov, M. and Webber, J. and Zhou, Y.},
	year = {1997},
	pmid = {9485492},
	keywords = {Models, Molecular, Peptide Mapping, Protein Conformation, Reproducibility of Results},
	pages = {29--37}
}

@article{berman_protein_2000,
	title = {The {Protein} {Data} {Bank}.},
	volume = {28},
	abstract = {The Protein Data Bank (PDB; http://www.rcsb.org/pdb/ ) is the single worldwide archive of structural data of biological macromolecules. This paper describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information, and near-term plans for the future development of the resource.},
	number = {1},
	journal = {Nucleic Acids Res.},
	author = {Berman, H M and Westbrook, J and Feng, Z and Gilliland, G and Bhat, T N and Weissig, H and Shindyalov, I N and Bourne, P E},
	month = jan,
	year = {2000},
	pages = {235--42}
}

@article{sayers_database_2010,
	title = {Database resources of the {National} {Center} for {Biotechnology} {Information}},
	volume = {38},
	journal = {Nucleic Acids Res.},
	author = {Sayers, E. W and Barrett, T and Benson, D. A and Bolton, E and Bryant, S. H and Canese, K and Chetvernin, V and Church, D. M and Dicuccio, M and Federhen, S and Feolo, M and Geer, L. Y and Helmberg, W and Kapustin, Y and Landsman, D and Lipman, D. J and Lu, Z and Madden, T. L and Madej, T and Maglott, D. R and Marchler-Bauer, A and Miller, V and Mizrachi, I and Ostell, J and Panchenko, A and Pruitt, K. D and Schuler, G. D and Sequeira, E and Sherry, S. T and Shumway, M and Sirotkin, K and Slotta, D and Souvorov, A and Starchenko, G and Tatusova, T. A and Wagner, L and Wang, Y and John Wilbur, W and Yaschenko, E and Ye},
	year = {2010},
	pages = {D5--16}
}

@article{needleman_general_1970,
	title = {A general method applicable to the search for similarities in the amino acid sequence of two proteins},
	volume = {48},
	issn = {0022-2836},
	language = {eng},
	number = {3},
	journal = {J. Mol. Biol.},
	author = {Needleman, S. B. and Wunsch, C. D.},
	month = mar,
	year = {1970},
	pmid = {5420325},
	keywords = {Amino Acid Sequence, Computers, Hemoglobins, Methods, Muramidase, Myoglobin, Probability, Ribonucleases},
	pages = {443--453}
}

@article{raj_yeast_2014,
	title = {Yeast {Alcohol} {Dehydrogenase} {Structure} and {Catalysis}},
	volume = {53},
	issn = {0006-2960},
	doi = {10.1021/bi5006442},
	abstract = {Yeast (Saccharomyces cerevisiae) alcohol dehydrogenase I (ADH1) is the constitutive enzyme that reduces acetaldehyde to ethanol during the fermentation of glucose. ADH1 is a homotetramer of subunits with 347 amino acid residues. A structure for ADH1 was determined by X-ray crystallography at 2.4 Å resolution. The asymmetric unit contains four different subunits, arranged as similar dimers named AB and CD. The unit cell contains two different tetramers made up of ?back-to-back? dimers, AB:AB and CD:CD. The A and C subunits in each dimer are structurally similar, with a closed conformation, bound coenzyme, and the oxygen of 2,2,2-trifluoroethanol ligated to the catalytic zinc in the classical tetrahedral coordination with Cys-43, Cys-153, and His-66. In contrast, the B and D subunits have an open conformation with no bound coenzyme, and the catalytic zinc has an alternative, inverted coordination with Cys-43, Cys-153, His-66, and the carboxylate of Glu-67. The asymmetry in the dimeric subunits of the tetramer provides two structures that appear to be relevant for the catalytic mechanism. The alternative coordination of the zinc may represent an intermediate in the mechanism of displacement of the zinc-bound water with alcohol or aldehyde substrates. Substitution of Glu-67 with Gln-67 decreases the catalytic efficiency by 100-fold. Previous studies of structural modeling, evolutionary relationships, substrate specificity, chemical modification, and site-directed mutagenesis are interpreted more fully with the three-dimensional structure.},
	number = {36},
	urldate = {2015-04-29},
	journal = {Biochemistry},
	author = {Raj, Savarimuthu Baskar and Ramaswamy, S. and Plapp, Bryce V.},
	month = sep,
	year = {2014},
	pages = {5791--5803}
}

@article{pervez_evaluating_2014,
	title = {Evaluating the accuracy and efficiency of multiple sequence alignment methods},
	volume = {10},
	doi = {10.4137/EBO.S19199},
	abstract = {A comparison of 10 most popular Multiple Sequence Alignment (MSA) tools, namely, MUSCLE, MAFFT(L-INS-i), MAFFT (FFT-NS-2), T-Coffee, ProbCons, SATe, Clustal Omega, Kalign, Multalin, and Dialign-TX is presented. We also focused on the significance of some implementations embedded in algorithm of each tool. Based on 10 simulated trees of different number of taxa generated by R, 400 known alignments and sequence files were constructed using indel-Seq-Gen. A total of 4000 test alignments were generated to study the effect of sequence length, indel size, deletion rate, and insertion rate. Results showed that alignment quality was highly dependent on the number of deletions and insertions in the sequences and that the sequence length and indel size had a weaker effect. Overall, ProbCons was consistently on the top of list of the evaluated MSA tools. SATe, being little less accurate, was 529.10\% faster than ProbCons and 236.72\% faster than MAFFT(L-INS-i). Among other tools, Kalign and MUSCLE achieved the highest sum of pairs. We also considered BALiBASE benchmark datasets and the results relative to BAliBASE- and indel-Seq-Gen-generated alignments were consistent in the most cases.},
	language = {eng},
	journal = {Evol. Bioinform. Online},
	author = {Pervez, Muhammad Tariq and Babar, Masroor Ellahi and Nadeem, Asif and Aslam, Muhammad and Awan, Ali Raza and Aslam, Naeem and Hussain, Tanveer and Naveed, Nasir and Qadri, Salman and Waheed, Usman and Shoaib, Muhammad},
	year = {2014},
	pmid = {25574120},
	pmcid = {PMC4267518},
	keywords = {column score, comparative study of MSA tools, evolutionary parameters, Multiple Sequence Alignment Tools, sum of pairs score},
	pages = {205--217}
}

@article{roy_i-tasser:_2010,
	title = {I-{TASSER}: a unified platform for automated protein structure and function prediction},
	volume = {5},
	number = {4},
	journal = {Nature Protocols},
	author = {Roy, Ambrish and Kucukural, Alper and Zhang, Yang},
	year = {2010},
	pages = {725--738}
}

@article{fredman_hgvbase:_2004,
	title = {{HGVbase}: a curated resource describing human {DNA} variation and phenotype relationships},
	volume = {32},
	journal = {Nucleic Acids Res.},
	author = {Fredman, D and Munns, G and Rios, D and Sjoholm, F and Siegfried, M and Lenhard, B and Lehvaslaiho, H and Brookes, A. J.},
	year = {2004},
	pages = {D516--519}
}

@article{jornvall_nomenclature_1995,
	title = {Nomenclature of alcohol dehydrogenases},
	volume = {30},
	number = {2},
	journal = {Alcohol Alcohol.},
	author = {Jörnvall, H and Höög, J-O},
	year = {1995},
	pages = {153--161}
}

@article{hogeweg_roots_2011,
	title = {The {Roots} of {Bioinformatics} in {Theoretical} {Biology}},
	volume = {7},
	issn = {1553-734X},
	doi = {10.1371/journal.pcbi.1002021},
	abstract = {From the late 1980s onward, the term “bioinformatics” mostly has been used to refer to computational methods for comparative analysis of genome data. However, the term was originally more widely defined as the study of informatic processes in biotic systems. In this essay, I will trace this early history (from a personal point of view) and I will argue that the original meaning of the term is re-emerging.},
	number = {3},
	urldate = {2017-03-21},
	journal = {PLoS Comput Biol},
	author = {Hogeweg, Paulien},
	month = mar,
	year = {2011},
	pmid = {21483479},
	pmcid = {PMC3068925},
	file = {PubMed Central Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/QMWCM5EW/Hogeweg - 2011 - The Roots of Bioinformatics in Theoretical Biology.pdf:application/pdf}
}

@article{zhang_protein_2009,
	title = {Protein structure prediction: when is it useful?},
	volume = {19},
	journal = {Curr. Op. Struc. Biol.},
	author = {Zhang, Yang},
	year = {2009},
	pages = {145--55}
}

@article{fiser_modeling_2000,
	title = {Modeling of loops in protein structures},
	volume = {9},
	issn = {0961-8368},
	doi = {10.1110/ps.9.9.1753},
	abstract = {Comparative protein structure prediction is limited mostly by the errors in alignment and loop modeling. We describe here a new automated modeling technique that significantly improves the accuracy of loop predictions in protein structures. The positions of all nonhydrogen atoms of the loop are optimized in a fixed environment with respect to a pseudo energy function. The energy is a sum of many spatial restraints that include the bond length, bond angle, and improper dihedral angle terms from the CHARMM-22 force field, statistical preferences for the main-chain and side-chain dihedral angles, and statistical preferences for nonbonded atomic contacts that depend on the two atom types, their distance through space, and separation in sequence. The energy function is optimized with the method of conjugate gradients combined with molecular dynamics and simulated annealing. Typically, the predicted loop conformation corresponds to the lowest energy conformation among 500 independent optimizations. Predictions were made for 40 loops of known structure at each length from 1 to 14 residues. The accuracy of loop predictions is evaluated as a function of thoroughness of conformational sampling, loop length, and structural properties of native loops. When accuracy is measured by local superposition of the model on the native loop, 100, 90, and 30\% of 4-, 8-, and 12-residue loop predictions, respectively, had {\textless}2 A RMSD error for the mainchain N, C(alpha), C, and O atoms; the average accuracies were 0.59 +/- 0.05, 1.16 +/- 0.10, and 2.61 +/- 0.16 A, respectively. To simulate real comparative modeling problems, the method was also evaluated by predicting loops of known structure in only approximately correct environments with errors typical of comparative modeling without misalignment. When the RMSD distortion of the main-chain stem atoms is 2.5 A, the average loop prediction error increased by 180, 25, and 3\% for 4-, 8-, and 12-residue loops, respectively. The accuracy of the lowest energy prediction for a given loop can be estimated from the structural variability among a number of low energy predictions. The relative value of the present method is gauged by (1) comparing it with one of the most successful previously described methods, and (2) describing its accuracy in recent blind predictions of protein structure. Finally, it is shown that the average accuracy of prediction is limited primarily by the accuracy of the energy function rather than by the extent of conformational sampling.},
	language = {eng},
	number = {9},
	journal = {Protein Sci.},
	author = {Fiser, A. and Do, R. K. and Sali, A.},
	month = sep,
	year = {2000},
	pmid = {11045621},
	pmcid = {PMC2144714},
	keywords = {Models, Molecular, Protein Conformation},
	pages = {1753--1773}
}

@article{lee_inhibition_2013,
	title = {Inhibition of human alcohol and aldehyde dehydrogenases by acetaminophen: {Assessment} of the effects on first-pass metabolism of ethanol},
	volume = {47},
	issn = {0741-8329},
	shorttitle = {Inhibition of human alcohol and aldehyde dehydrogenases by acetaminophen},
	doi = {10.1016/j.alcohol.2013.09.001},
	abstract = {Acetaminophen is one of the most widely used over-the-counter analgesic, antipyretic medications. Use of acetaminophen and alcohol are commonly associated. Previous studies showed that acetaminophen might affect bioavailability of ethanol by inhibiting gastric alcohol dehydrogenase (ADH). However, potential inhibitions by acetaminophen of first-pass metabolism (FPM) of ethanol, catalyzed by the human ADH family and by relevant aldehyde dehydrogenase (ALDH) isozymes, remain undefined. ADH and ALDH both exhibit racially distinct allozymes and tissue-specific distribution of isozymes, and are principal enzymes responsible for ethanol metabolism in humans. In this study, we investigated acetaminophen inhibition of ethanol oxidation with recombinant human ADH1A, ADH1B1, ADH1B2, ADH1B3, ADH1C1, ADH1C2, ADH2, and ADH4, and inhibition of acetaldehyde oxidation with recombinant human ALDH1A1 and ALDH2. The investigations were done at near physiological pH 7.5 and with a cytoplasmic coenzyme concentration of 0.5 mm NAD+. Acetaminophen acted as a noncompetitive inhibitor for ADH enzymes, with the slope inhibition constants (Kis) ranging from 0.90 mm (ADH2) to 20 mm (ADH1A), and the intercept inhibition constants (Kii) ranging from 1.4 mm (ADH1C allozymes) to 19 mm (ADH1A). Acetaminophen exhibited noncompetitive inhibition for ALDH2 (Kis = 3.0 mm and Kii = 2.2 mm), but competitive inhibition for ALDH1A1 (Kis = 0.96 mm). The metabolic interactions between acetaminophen and ethanol/acetaldehyde were assessed by computer simulation using inhibition equations and the determined kinetic constants. At therapeutic to subtoxic plasma levels of acetaminophen (i.e., 0.2–0.5 mm) and physiologically relevant concentrations of ethanol (10 mm) and acetaldehyde (10 μm) in target tissues, acetaminophen could inhibit ADH1C allozymes (12–26\%) and ADH2 (14–28\%) in the liver and small intestine, ADH4 (15–31\%) in the stomach, and ALDH1A1 (16–33\%) and ALDH2 (8.3–19\%) in all 3 tissues. The results suggest that inhibition by acetaminophen of hepatic and gastrointestinal FPM of ethanol through ADH and ALDH pathways might become significant at higher, subtoxic levels of acetaminophen.},
	number = {7},
	urldate = {2014-12-09},
	journal = {Alcohol},
	author = {Lee, Yung-Pin and Liao, Jian-Tong and Cheng, Ya-Wen and Wu, Ting-Lun and Lee, Shou-Lun and Liu, Jong-Kang and Yin, Shih-Jiun},
	month = nov,
	year = {2013},
	keywords = {Acetaminophen, Alcohol Dehydrogenase, Aldehyde dehydrogenase, Ethanol, First-pass metabolism of ethanol, Inhibition kinetics, Metabolic interaction},
	pages = {559--565}
}

@article{tateno_dna_2002,
	title = {{DNA} {Data} {Bank} of {Japan} ({DDBJ}) for genome scale research in life science},
	volume = {30},
	issn = {1362-4962},
	abstract = {The DNA Data Bank of Japan (DDBJ, http://www.ddbj.nig.ac.jp) has made an effort to collect as much data as possible mainly from Japanese researchers. The increase rates of the data we collected, annotated and released to the public in the past year are 43\% for the number of entries and 52\% for the number of bases. The increase rates are accelerated even after the human genome was sequenced, because sequencing technology has been remarkably advanced and simplified, and research in life science has been shifted from the gene scale to the genome scale. In addition, we have developed the Genome Information Broker (GIB, http://gib.genes.nig.ac.jp) that now includes more than 50 complete microbial genome and Arabidopsis genome data. We have also developed a database of the human genome, the Human Genomics Studio (HGS, http://studio.nig.ac.jp). HGS provides one with a set of sequences being as continuous as possible in any one of the 24 chromosomes. Both GIB and HGS have been updated incorporating newly available data and retrieval tools.},
	language = {eng},
	number = {1},
	journal = {Nucleic Acids Res.},
	author = {Tateno, Y. and Imanishi, T. and Miyazaki, S. and Fukami-Kobayashi, K. and Saitou, N. and Sugawara, H. and Gojobori, T.},
	month = jan,
	year = {2002},
	pmid = {11752245},
	pmcid = {PMC99140},
	keywords = {Animals, Arabidopsis, Base Sequence, Biological Science Disciplines, Databases, Nucleic Acid, Data Collection, Genome, Genome, Bacterial, Genome, Human, Genome, Plant, Humans, Japan, Sequence Analysis, DNA},
	pages = {27--30}
}

@article{jelokova_features_1994,
	title = {Features of structural zinc in mammalian alcohol dehydrogenase. {Site}-directed mutagenesis of the zinc ligands},
	volume = {225},
	issn = {0014-2956},
	abstract = {All four cysteine ligands to the structural zinc atom of human class-I and class-III alcohol dehydrogenase have been exchanged by site-directed mutagenesis in order to study the importance of the metal in the mammalian enzymes. The cysteine residues were replaced with Ala and Ser, residues that are not able to ligand zinc. All mutations resulted in inactive, unstable enzymes, in contrast to the non-mutated human alcohol dehydrogenases that are easily isolated. Northern-blot analysis revealed the presence of the expected mRNAs from expression plasmids constructed with the different mutated and non-mutated alcohol dehydrogenases, and Western-blot analysis gave faint signals for the mutated recombinant proteins from crude extracts. This verifies that the plasmid constructs are correct, but that the translated, mutated proteins lacking the zinc-stabilized local fold, are subject to rapid degradation. Hence, the results directly illustrate the importance of the structural zinc atom in mammalian alcohol dehydrogenase and confirm it as a component with 'structural' properties. The results are compatible with those from sensitivities to proteases and from the structures of other proteins within the super-family, indicating that the structural role of the zinc atom may involve conservation of interfaces regulating the enzyme quaternary structure.},
	language = {eng},
	number = {3},
	journal = {Eur. J. Biochem.},
	author = {Jeloková, J. and Karlsson, C. and Estonius, M. and Jörnvall, H. and Höög, J-O},
	month = nov,
	year = {1994},
	pmid = {7957193},
	keywords = {Alcohol Dehydrogenase, Amino Acid Sequence, Base Sequence, Binding Sites, Cloning, Molecular, Cysteine, DNA Primers, Escherichia coli, Humans, Ligands, Molecular Sequence Data, Mutagenesis, Site-Directed, Protein Conformation, Recombinant Proteins, RNA, Messenger, Zinc},
	pages = {1015--1019}
}

@article{kabsch_dictionary_1983,
	title = {Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features},
	volume = {22},
	number = {12},
	journal = {J. Mol. Biol.},
	author = {Kabsch, W and Sander, C.},
	year = {1983},
	pages = {2577--2637}
}

@article{aken_ensembl_2017,
	title = {Ensembl 2017},
	volume = {45},
	issn = {1362-4962},
	doi = {10.1093/nar/gkw1104},
	abstract = {Ensembl (www.ensembl.org) is a database and genome browser for enabling research on vertebrate genomes. We import, analyse, curate and integrate a diverse collection of large-scale reference data to create a more comprehensive view of genome biology than would be possible from any individual dataset. Our extensive data resources include evidence-based gene and regulatory region annotation, genome variation and gene trees. An accompanying suite of tools, infrastructure and programmatic access methods ensure uniform data analysis and distribution for all supported species. Together, these provide a comprehensive solution for large-scale and targeted genomics applications alike. Among many other developments over the past year, we have improved our resources for gene regulation and comparative genomics, and added CRISPR/Cas9 target sites. We released new browser functionality and tools, including improved filtering and prioritization of genome variation, Manhattan plot visualization for linkage disequilibrium and eQTL data, and an ontology search for phenotypes, traits and disease. We have also enhanced data discovery and access with a track hub registry and a selection of new REST end points. All Ensembl data are freely released to the scientific community and our source code is available via the open source Apache 2.0 license.},
	language = {eng},
	number = {D1},
	journal = {Nucleic Acids Res.},
	author = {Aken, Bronwen L. and Achuthan, Premanand and Akanni, Wasiu and Amode, M. Ridwan and Bernsdorff, Friederike and Bhai, Jyothish and Billis, Konstantinos and Carvalho-Silva, Denise and Cummins, Carla and Clapham, Peter and Gil, Laurent and Girón, Carlos García and Gordon, Leo and Hourlier, Thibaut and Hunt, Sarah E. and Janacek, Sophie H. and Juettemann, Thomas and Keenan, Stephen and Laird, Matthew R. and Lavidas, Ilias and Maurel, Thomas and McLaren, William and Moore, Benjamin and Murphy, Daniel N. and Nag, Rishi and Newman, Victoria and Nuhn, Michael and Ong, Chuang Kee and Parker, Anne and Patricio, Mateus and Riat, Harpreet Singh and Sheppard, Daniel and Sparrow, Helen and Taylor, Kieron and Thormann, Anja and Vullo, Alessandro and Walts, Brandon and Wilder, Steven P. and Zadissa, Amonida and Kostadima, Myrto and Martin, Fergal J. and Muffato, Matthieu and Perry, Emily and Ruffier, Magali and Staines, Daniel M. and Trevanion, Stephen J. and Cunningham, Fiona and Yates, Andrew and Zerbino, Daniel R. and Flicek, Paul},
	month = jan,
	year = {2017},
	pmid = {27899575},
	pmcid = {PMC5210575},
	pages = {D635--D642}
}

@article{hoog_mammalian_2003,
	title = {The mammalian alcohol dehydrogenases interact in several metabolic pathways},
	volume = {143–144},
	issn = {0009-2797},
	shorttitle = {Enzymology and {Molecular} {Biology} of {Carbonyl} {Metabolism} - 11th {International} {Workshop}.},
	doi = {10.1016/S0009-2797(02)00225-9},
	abstract = {Mammalian alcohol dehydrogenases (ADHs), including ADH1–ADH5/6, interact extensively in the oxidation and reduction of alcohols and aldehydes. ADH1 and ADH2 are involved in several metabolic pathways besides the oxidation of ethanol and have also been shown to be involved in drug transformations. The ADH2 enzymes show further complexity among the species, e.g. in enzymatic characteristics where the rodent forms essentially lack ethanol-oxidizing capacity. ADH3 (glutathione-dependent formaldehyde dehydrogenase) has been shown to catalyze the reductive breakdown of S-nitrosoglutathione, indicating involvement in nitric oxide metabolism. Mass spectrometry identified the major enzymatic product as glutathione sulfinamide. This reductive breakdown directly interferes with the formaldehyde scavenging that has been proposed to be the physiological action of ADH3. The human ADH5 and rodent ADH6 seem to be the corresponding enzymes due to their similar behavior. None of these latter ADHs have so far been assigned to any function. They can be expressed as recombinant proteins but no enzymatic activity has been detected.},
	urldate = {2013-08-26},
	journal = {Chemico-Biological Interactions},
	author = {Höög, Jan-Olov and Strömberg, Patrik and Hedberg, Jesper J and Griffiths, William J},
	month = feb,
	year = {2003},
	keywords = {Alcohol Dehydrogenase, Evolution, Metabolic interaction, Nitrosoglutathione},
	pages = {175--181},
	file = {ScienceDirect Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/C8NQWEQH/Höög et al. - 2003 - The mammalian alcohol dehydrogenases interact in s.pdf:application/pdf;ScienceDirect Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/QAKT59E6/S0009279702002259.html:text/html}
}

@article{abraham_gromacs:_2015,
	title = {{GROMACS}: {High} performance molecular simulations through multi-level parallelism from laptops to supercomputers},
	volume = {1–2},
	issn = {2352-7110},
	shorttitle = {{GROMACS}},
	doi = {10.1016/j.softx.2015.06.001},
	abstract = {GROMACS is one of the most widely used open-source and free software codes in chemistry, used primarily for dynamical simulations of biomolecules. It provides a rich set of calculation types, preparation and analysis tools. Several advanced techniques for free-energy calculations are supported. In version 5, it reaches new performance heights, through several new and enhanced parallelization algorithms. These work on every level; SIMD registers inside cores, multithreading, heterogeneous CPU–GPU acceleration, state-of-the-art 3D domain decomposition, and ensemble-level parallelization through built-in replica exchange and the separate Copernicus framework. The latest best-in-class compressed trajectory storage format is supported.},
	urldate = {2017-04-02},
	journal = {SoftwareX},
	author = {Abraham, Mark James and Murtola, Teemu and Schulz, Roland and Páll, Szilárd and Smith, Jeremy C. and Hess, Berk and Lindahl, Erik},
	month = sep,
	year = {2015},
	keywords = {Free energy, GPU, Molecular dynamics, SIMD},
	pages = {19--25},
	file = {ScienceDirect Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/AZWS8XUF/Abraham et al. - 2015 - GROMACS High performance molecular simulations th.pdf:application/pdf;ScienceDirect Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/EQQGSHB3/S2352711015000059.html:text/html}
}

@article{packer_snp500cancer:_2004,
	title = {{SNP}500Cancer: a public resource for sequence validation and assay development for genetic variation in candidate genes},
	volume = {32},
	journal = {Nucleic Acids Res.},
	author = {Packer, B. R. and Yeager, M. and Staats, B. and Welch, R. and Crenshaw, A. and Kiley, M. and Eckert, A. and Beerman, M. and Miller, E. and Bergen, A. and Rothman, N. and Strausberg, R. and Chanock, S. J.},
	year = {2004},
	pages = {D528--532}
}

@misc{noauthor_rcsb_nodate,
	title = {{RCSB} {PDB} - {Content} {Growth} {Report}},
	url = {http://www.rcsb.org/pdb/statistics/contentGrowthChart.do?content=total&seqid=100},
	urldate = {2017-05-02},
	file = {RCSB PDB - Content Growth Report:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/J6BB7A6M/contentGrowthChart.html:text/html}
}

@article{chen_structural_2008,
	title = {Structural {Enzymological} {Studies} of 2-{Enoyl} {Thioester} {Reductase} of the {Human} {Mitochondrial} {FAS} {II} {Pathway}: {New} {Insights} into {Its} {Substrate} {Recognition} {Properties}},
	volume = {379},
	issn = {0022-2836},
	shorttitle = {Structural {Enzymological} {Studies} of 2-{Enoyl} {Thioester} {Reductase} of the {Human} {Mitochondrial} {FAS} {II} {Pathway}},
	doi = {10.1016/j.jmb.2008.04.041},
	abstract = {Structural and kinetic properties of the human 2-enoyl thioester reductase [mitochondrial enoyl–coenzyme A reductase (MECR)/ETR1] of the mitochondrial fatty acid synthesis (FAS) II pathway have been determined. The crystal structure of this dimeric enzyme (at 2.4 Å resolution) suggests that the binding site for the recognition helix of the acyl carrier protein is in a groove between the two adjacent monomers. This groove is connected via the pantetheine binding cleft to the active site. The modeled mode of NADPH binding, using molecular dynamics calculations, suggests that Tyr94 and Trp311 are critical for catalysis, which is supported by enzyme kinetic data. A deep, water-filled pocket, shaped by hydrophobic and polar residues and extending away from the catalytic site, was recognized. This pocket can accommodate a fatty acyl tail of up to 16 carbons. Mutagenesis of the residues near the end of this pocket confirms the importance of this region for the binding of substrate molecules with long fatty acyl tails. Furthermore, the kinetic analysis of the wild-type MECR/ETR1 shows a bimodal distribution of catalytic efficiencies, in agreement with the notion that two major products are generated by the mitochondrial FAS II pathway.},
	number = {4},
	urldate = {2013-08-26},
	journal = {Journal of Molecular Biology},
	author = {Chen, Zhi-Jun and Pudas, Regina and Sharma, Satyan and Smart, Oliver S. and Juffer, André H. and Hiltunen, J. Kalervo and Wierenga, Rik K. and Haapalainen, Antti M.},
	month = jun,
	year = {2008},
	keywords = {ACP, CoA, ETR, FAS, MDR},
	pages = {830--844},
	file = {ScienceDirect Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/CWVSUFM7/Chen et al. - 2008 - Structural Enzymological Studies of 2-Enoyl Thioes.pdf:application/pdf;ScienceDirect Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/4VUFQDJR/S0022283608004889.html:text/html;Structural enzymological studies of 2-enoyl thioester reductase of the human mitochondrial FAS... - Abstract - Europe PubMed Central:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/9CMMF5D7/reload=0\;jsessionid=s5Z0gbcXo3Gz76pv1GAu.html:text/html}
}

@article{brandt_molecular_2009,
	title = {Molecular dynamics study of zinc binding to cysteines in a peptide mimic of the alcohol dehydrogenase structural zinc site},
	volume = {11},
	issn = {1463-9084},
	doi = {10.1039/B815482A},
	abstract = {The binding of zinc (Zn) ions to proteins is important for many cellular events. The theoretical and computational description of this binding (as well as that of other transition metals) is a challenging task. In this paper the binding of the Zn ion to four cysteine residues in the structural site of horse liver alcohol dehydrogenase (HLADH) is studied using a synthetic peptide mimic of this site. The study includes experimental measurements of binding constants, classical free energy calculations from molecular dynamics (MD) simulations and quantum mechanical (QM) electron structure calculations. The classical MD results account for interactions at the molecular level and reproduce the absolute binding energy and the hydration free energy of the Zn ion with an accuracy of about 10\%. This is insufficient to obtain correct free energy differences. QM correction terms were calculated from density functional theory (DFT) on small clusters of atoms to include electronic polarisation of the closest waters and covalent contributions to the Zn–S coordination bond. This results in reasonably good agreement with the experimentally measured binding constants and Zn ion hydration free energies in agreement with published experimental values. The study also includes the replacement of one cysteine residue to an alanine. Simulations as well as experiments showed only a small effect of this upon the binding free energy. A detailed analysis indicate that the sulfur is replaced by three water molecules, thereby changing the coordination number of Zn from four (as in the original peptide) to six (as in water).},
	language = {en},
	number = {6},
	urldate = {2015-04-28},
	journal = {Phys. Chem. Chem. Phys.},
	author = {Brandt, Erik G. and Hellgren, Mikko and Brinck, Tore and Bergman, Tomas and Edholm, Olle},
	month = jan,
	year = {2009},
	pages = {975--983}
}

@article{gonzalez-duarte_merging_2005,
	title = {Merging protein, gene and genomic data: the evolution of the {MDR}-{ADH} family},
	volume = {95},
	journal = {Heredity},
	author = {Gonzàlez-Duarte, R and Albalat, R},
	year = {2005},
	pages = {184--97}
}

@article{zhang_scoring_2004,
	title = {Scoring function for automated assessment of protein structure template quality},
	volume = {57},
	issn = {1097-0134},
	doi = {10.1002/prot.20264},
	abstract = {We have developed a new scoring function, the template modeling score (TM-score), to assess the quality of protein structure templates and predicted full-length models by extending the approaches used in Global Distance Test (GDT)1 and MaxSub.2 First, a protein size-dependent scale is exploited to eliminate the inherent protein size dependence of the previous scores and appropriately account for random protein structure pairs. Second, rather than setting specific distance cutoffs and calculating only the fractions with errors below the cutoff, all residue pairs in alignment/modeling are evaluated in the proposed score. For comparison of various scoring functions, we have constructed a large-scale benchmark set of structure templates for 1489 small to medium size proteins using the threading program PROSPECTOR\_3 and built the full-length models using MODELLER and TASSER. The TM-score of the initial threading alignments, compared to the GDT and MaxSub scoring functions, shows a much stronger correlation to the quality of the final full-length models. The TM-score is further exploited as an assessment of all 'new fold' targets in the recent CASP5 experiment and shows a close coincidence with the results of human-expert visual assessment. These data suggest that the TM-score is a useful complement to the fully automated assessment of protein structure predictions. The executable program of TM-score is freely downloadable at http://bioinformatics.buffalo.edu/TM-score.},
	language = {eng},
	number = {4},
	journal = {Proteins},
	author = {Zhang, Yang and Skolnick, Jeffrey},
	month = dec,
	year = {2004},
	pmid = {15476259},
	keywords = {Automation, Benchmarking, Computational Biology, Databases, Protein, Models, Molecular, Protein Folding, Proteins, Protein Structure, Tertiary, Sequence Alignment, Structural Homology, Protein},
	pages = {702--710}
}

@article{eklund_three-dimensional_1976,
	title = {Three-dimensional structure of horse liver alcohol dehydrogenase at 2.4 Å resolution},
	volume = {102},
	issn = {0022-2836},
	language = {eng},
	number = {1},
	journal = {J. Mol. Biol.},
	author = {Eklund, H. and Nordström, B. and Zeppezauer, E. and Söderlund, G. and Ohlsson, I. and Boiwe, T. and Söderberg, B. O. and Tapia, O. and Brändén, C. I. and Akeson, A.},
	month = mar,
	year = {1976},
	pmid = {178875},
	keywords = {Adenine, Adenosine Diphosphate Sugars, Alcohol Oxidoreductases, Animals, Binding Sites, Diphosphates, Fourier Analysis, Horses, Liver, Models, Molecular, Niacinamide, Protein Binding, Protein Conformation, Ribose, X-Ray Diffraction},
	pages = {27--59}
}

@article{barker_4273:_2013,
	title = {4273π: {Bioinformatics} education on low cost {ARM} hardware},
	volume = {14},
	copyright = {2013 Barker et al.; licensee BioMed Central Ltd.},
	issn = {1471-2105},
	shorttitle = {4273π},
	doi = {10.1186/1471-2105-14-243},
	abstract = {Teaching bioinformatics at universities is complicated by typical computer classroom settings. As well as running software locally and online, students should gain experience of systems administration. For a future career in biology or bioinformatics, the installation of software is a useful skill. We propose that this may be taught by running the course on GNU/Linux running on inexpensive Raspberry Pi computer hardware, for which students may be granted full administrator access.},
	language = {en},
	number = {1},
	urldate = {2013-09-12},
	journal = {BMC Bioinformatics},
	author = {Barker, Daniel and Ferrier, David EK and Holland, Peter WH and Mitchell, John BO and Plaisier, Heleen and Ritchie, Michael G. and Smart, Steven D.},
	month = aug,
	year = {2013},
	pmid = {23937194},
	keywords = {Bioinformatics education, Linux, Raspberry Pi, Teaching material},
	pages = {243},
	file = {Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/JEFD33MP/Barker et al. - 2013 - 4273π Bioinformatics education on low cost ARM ha.pdf:application/pdf;Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/UH93DANC/Barker et al. - 2013 - 4273π Bioinformatics education on low cost ARM ha.html:text/html}
}

@article{negelein_kristallisation_1937,
	title = {Kristallisation des {Proteins} der {Acetaldehydereduktase}},
	volume = {289},
	journal = {Biochem. Zeit.},
	author = {Negelein, E and Wulff, H-J},
	year = {1937},
	pages = {436--437}
}

@article{stoop_purification_1995,
	title = {Purification of {NAD}-dependent mannitol dehydrogenase from celery suspension cultures},
	volume = {108},
	issn = {0032-0889},
	abstract = {Mannitol dehydrogenase, a mannitol:mannose 1-oxidoreductase, constitutes the first enzymatic step in the catabolism of mannitol in nonphotosynthetic tissues of celery (Apium graveolens L.). Endogenous regulation on the enzyme activity in response to environmental cues is critical in modulating tissue concentration of mannitol, which, importantly, contribute to stress tolerance of celery. The enzyme was purified to homogeneity from celery suspension cultures grown on D-mannitol as the carbon source. Mannitol dehydrogenase was purified 589-fold to a specific activity of 365 mumol h-1 mg-1 protein with a 37\% yield of enzyme activity present in the crude extract. A highly efficient and simple purification protocol was developed involving polyethylene glycol fractionation, diethylaminoethyl-anion-exchange chromatography, and NAD-agarose affinity chromatography using NAD gradient elution. Sodium dodecylsulfate gel electrophoresis of the final preparation revealed a single 40-kD protein. The molecular mass of the native protein was determined to be approximately 43 kD, indicating that the enzyme is a monomer. Polyclonal antibodies raised against the enzyme inhibited enzymatic activity of purified mannitol dehydrogenase. Immunoblots of crude protein extracts from mannitol-grown celery cells and sink tissues of celery, celeriac, and parsley subjected to sodium dodecyl sulfate gel electrophoresis showed a single major immuno-reactive 40-kD protein.},
	language = {eng},
	number = {3},
	journal = {Plant Physiol.},
	author = {Stoop, J. M. and Williamson, J. D. and Conkling, M. A. and Pharr, D. M.},
	month = jul,
	year = {1995},
	pmid = {7630943},
	pmcid = {PMC157476},
	keywords = {Amino Acid Sequence, Cells, Cultured, Chromatography, Ion Exchange, Molecular Sequence Data, NAD, Sugar Alcohol Dehydrogenases, Vegetables},
	pages = {1219--1225}
}

@article{essman_smooth_1995,
	title = {A smooth particle mesh {Ewald} method},
	volume = {103},
	journal = {J. Chem. Phys.},
	author = {Essman, U and Perela, L and Berkowitz, M L and Darden, T and Lee, H and Pedersen, L G},
	year = {1995},
	pages = {8577--8592}
}

@article{taneja_conserved_1999,
	title = {Conserved structural features and sequence patterns in the {GroES} fold family},
	volume = {12},
	issn = {0269-2139},
	abstract = {An irregular, all beta-class of proteins, comprising members of the chaperonin-10, quinone oxidoreductase, glucose dehydrogenase and alcohol dehydrogenase families has earlier been classified as the GroES fold. In this communication, we present an extensive analysis of sequences and three dimensional structures of proteins belonging to this family. The individual protein structures can be superposed within 1.6 A for more than 60 structurally equivalent residues. The comparisons show a highly conserved hydrophobic core and conservation of a few key residues. A glycyl-aspartate dipeptide is suggested as being critical for the maintenance of the GroES fold. One of the surprising findings of the study is the non-conservative nature of Ile to Leu mutations in the protein core, although Ile to Val mutations are found to occur frequently.},
	language = {eng},
	number = {10},
	journal = {Protein Eng.},
	author = {Taneja, B. and Mande, S. C.},
	month = oct,
	year = {1999},
	pmid = {10556240},
	keywords = {Alcohol Dehydrogenase, Amino Acid Sequence, Chaperonin 10, Conserved Sequence, Glucose Dehydrogenases, Models, Molecular, Molecular Sequence Data, Mutation, Oxidoreductases, Protein Folding, Proteins, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Structure-Activity Relationship},
	pages = {815--818}
}

@article{marks_protein_2011,
	title = {Protein 3D {Structure} {Computed} from {Evolutionary} {Sequence} {Variation}},
	volume = {6},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0028766},
	abstract = {The evolutionary trajectory of a protein through sequence space is constrained by its function. Collections of sequence homologs record the outcomes of millions of evolutionary experiments in which the protein evolves according to these constraints. Deciphering the evolutionary record held in these sequences and exploiting it for predictive and engineering purposes presents a formidable challenge. The potential benefit of solving this challenge is amplified by the advent of inexpensive high-throughput genomic sequencing., In this paper we ask whether we can infer evolutionary constraints from a set of sequence homologs of a protein. The challenge is to distinguish true co-evolution couplings from the noisy set of observed correlations. We address this challenge using a maximum entropy model of the protein sequence, constrained by the statistics of the multiple sequence alignment, to infer residue pair couplings. Surprisingly, we find that the strength of these inferred couplings is an excellent predictor of residue-residue proximity in folded structures. Indeed, the top-scoring residue couplings are sufficiently accurate and well-distributed to define the 3D protein fold with remarkable accuracy., We quantify this observation by computing, from sequence alone, all-atom 3D structures of fifteen test proteins from different fold classes, ranging in size from 50 to 260 residues., including a G-protein coupled receptor. These blinded inferences are de novo, i.e., they do not use homology modeling or sequence-similar fragments from known structures. The co-evolution signals provide sufficient information to determine accurate 3D protein structure to 2.7–4.8 Å C$\alpha$-RMSD error relative to the observed structure, over at least two-thirds of the protein (method called EVfold, details at http://EVfold.org). This discovery provides insight into essential interactions constraining protein evolution and will facilitate a comprehensive survey of the universe of protein structures, new strategies in protein and drug design, and the identification of functional genetic variants in normal and disease genomes.},
	number = {12},
	urldate = {2017-03-21},
	journal = {PLoS One},
	author = {Marks, Debora S. and Colwell, Lucy J. and Sheridan, Robert and Hopf, Thomas A. and Pagnani, Andrea and Zecchina, Riccardo and Sander, Chris},
	month = dec,
	year = {2011},
	pmid = {22163331},
	pmcid = {PMC3233603},
	file = {PubMed Central Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/8DM9ABC2/Marks et al. - 2011 - Protein 3D Structure Computed from Evolutionary Se.pdf:application/pdf}
}

@article{bottegoni_four-dimensional_2009,
	title = {Four-dimensional docking: a fast and accurate account of discrete receptor flexibility in ligand docking},
	volume = {52},
	journal = {Journal of Medical Chemistry},
	author = {Bottegoni, G. and Kufareva, I. and Totrov, M. and Abagyan, R},
	year = {2009},
	pages = {397--406}
}

@article{zhang_spicker:_2003,
	title = {{SPICKER}: {A} {Clustering} {Approach} to {Identify} {Near}-{Native} {Protein} {Folds}},
	volume = {25},
	journal = {J. Comp. Chem.},
	author = {Zhang, Yang and Skolnick, Jeffrey},
	year = {2003},
	pages = {865--871}
}

@article{yu_prostaglandin_2013,
	title = {Prostaglandin reductase-3 negatively modulates adipogenesis through regulation of {PPAR$\gamma$} activity},
	volume = {54},
	issn = {1539-7262},
	doi = {10.1194/jlr.M037556},
	abstract = {Adipocyte differentiation is a multistep program under regulation by several factors. Peroxisome proliferator-activated receptor $\gamma$ (PPAR$\gamma$) serves as a master regulator of adipogenesis. However, the endogenous ligand for PPAR$\gamma$ remained elusive until 15-keto-PGE2 was identified recently as an endogenous PPAR$\gamma$ ligand. In this study, we demonstrate that zinc-containing alcohol dehydrogenase 2 (ZADH2; here termed prostaglandin reductase-3, PTGR-3) is a new member of prostaglandin reductase family that converts 15-keto-PGE2 to 13,14-dihydro-15-keto-PGE2. Adipogenesis is accelerated when endogenous PTGR-3 is silenced in 3T3-L1 preadipocytes, whereas forced expression of PTGR-3 significantly decreases adipogenesis. PTGR-3 expression decreased during adipocyte differentiation, accompanied by an increased level of 15-keto-PGE2. 15-keto-PGE2 exerts a potent proadipogenic effect by enhancing PPAR$\gamma$ activity, whereas overexpression of PTGR-3 in 3T3-L1 preadipocytes markedly suppressed the proadipogenic effect of 15-keto-PGE2 by repressing PPAR$\gamma$ activity. Taken together, these findings demonstrate for the first time that PTGR-3 is a novel 15-oxoprostaglandin-Δ(13)-reductase and plays a critical role in modulation of normal adipocyte differentiation via regulation of PPAR$\gamma$ activity. Thus, modulation of PTGR-3 might provide a novel avenue for treating obesity and related metabolic disorders.},
	language = {eng},
	number = {9},
	journal = {J. Lipid Res.},
	author = {Yu, Yu-Hsiang and Chang, Yi-Cheng and Su, Tseng-Hsiung and Nong, Jiun-Yi and Li, Chao-Chin and Chuang, Lee-Ming},
	month = sep,
	year = {2013},
	pmid = {23821743},
	pmcid = {PMC3735937},
	keywords = {adipocyte differentiation, Adipocytes, Adipogenesis, Adipose Tissue, White, Adiposity, Animals, Cell Line, Dinoprostone, eicosanoid, ligand, Mice, nuclear receptor, Obesity, Oxidoreductases Acting on CH-CH Group Donors, PPAR gamma},
	pages = {2391--2399}
}

@article{miyamoto_settle:_1992,
	title = {{SETTLE}: {An} analytical version of the {SHAKE} and {RATTLE} algorithms for rigid water models},
	volume = {13},
	journal = {J. Comp. Chem.},
	author = {Miyamoto, S and Kollman, P A},
	year = {1992},
	pages = {952--962}
}

@article{ohta_variation_1995,
	title = {Variation in synonymous substitution rates among mammalian genes and the correlation between synonymous and nonsynonymous divergences},
	volume = {41},
	issn = {0022-2844},
	abstract = {Using mammalian gene sequences, the variances in the numbers of synonymous and nonsynonymous substitutions among genes were estimated together with the correlation coefficient between the two. The expected correlation coefficient can be obtained under the neutral theory using these estimated values of the variances. The expected coefficient is found to often be one-half to two-thirds of the observed value. Possible causes for the disagreement were discussed, such as correlated selective constraints on the two types of substitutions and excess doublet mutations. The variance of mutation rate and that of selective constraint were also estimated. The results show that the coefficient of variation of the former is 0.2-0.3, whereas that of the latter is 0.7-0.9.},
	language = {eng},
	number = {6},
	journal = {J Mol Evol},
	author = {Ohta, T. and Ina, Y.},
	month = dec,
	year = {1995},
	pmid = {8587116},
	keywords = {Animals, Base Sequence, Evolution, Molecular, Genes, Humans, Models, Theoretical, Sequence analysis},
	pages = {717--720}
}

@article{yokomizo_cdna_1996,
	title = {{cDNA} cloning, expression, and mutagenesis study of leukotriene {B}4 12-hydroxydehydrogenase},
	volume = {271},
	issn = {0021-9258},
	abstract = {Leukotriene B4 12-hydroxydehydrogenase catalyzes the conversion of leukotriene B4 into its biologically less active metabolite, 12-oxo-leukotriene B4. This is an initial and key step of metabolic inactivation of leukotriene B4 in various tissues other than leukocytes. Here we report the cDNA cloning for porcine and human enzymes from kidney cDNA libraries. A full-length cDNA of the porcine enzyme contains an open reading frame consisting of 987 base pairs, corresponding to 329 amino acids. The human enzyme showed a 97.1\% homology with the porcine enzyme. Northern blotting of human tissues revealed its high expression in the kidney, liver, and intestine but not in leukocytes. The porcine enzyme was expressed as a glutathione S-transferase fusion protein in Escherichia coli, which exhibited similar characteristics with the native enzyme. Because the enzymes have a homology, in part, with NAD(P)(+)-dependent alcohol dehydrogenases, a site-directed mutagenesis study was carried out. We found that three glycines at 152, 155, and 166 have crucial roles in the enzyme activity, possibly by producing an NADP+ binding pocket.},
	language = {eng},
	number = {5},
	journal = {J. Biol. Chem.},
	author = {Yokomizo, T. and Ogawa, Y. and Uozumi, N. and Kume, K. and Izumi, T. and Shimizu, T.},
	month = feb,
	year = {1996},
	pmid = {8576264},
	keywords = {Alcohol Oxidoreductases, Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Cloning, Molecular, DNA, Complementary, DNA Primers, Glutathione Transferase, Humans, Molecular Sequence Data, Mutagenesis, Site-Directed, NADP, Recombinant Fusion Proteins, Sequence Homology, Amino Acid, Swine},
	pages = {2844--2850}
}

@article{fernandez_human_2007,
	title = {Human and yeast zeta-crystallins bind {AU}-rich elements in {RNA}},
	volume = {64},
	issn = {1420-682X},
	doi = {10.1007/s00018-007-7091-1},
	abstract = {Zeta-crystallins constitute a family of proteins with NADPH:quinone reductase activity found initially in mammalian lenses but now known to be present in many other organisms and tissues. Few proteins from this family have been characterized, and their function remains unclear. In the present work, zeta-crystallins from human and yeast (Zta1p) were expressed, purified and characterized. Both enzymes are able to reduce ortho-quinones in the presence of NADPH but are not active with 2-alkenals. Deletion of the ZTA1 gene makes yeast more sensitive to menadione and hydrogen peroxide, suggesting a role in the oxidative stress response. The human and yeast enzymes specifically bind to adenine-uracil rich elements (ARE) in RNA, indicating that both enzymes are ARE-binding proteins and that this property has been conserved in zeta-crystallins throughout evolution. This supports a role for zeta-crystallins as trans-acting factors that could regulate the turnover of certain mRNAs.},
	language = {eng},
	number = {11},
	journal = {Cell. Mol. Life Sci.},
	author = {Fernández, M. R. and Porté, S. and Crosas, E. and Barberà, N. and Farrés, J. and Biosca, J. A. and Parés, X.},
	month = jun,
	year = {2007},
	pmid = {17497241},
	keywords = {Animals, Base Sequence, Humans, Molecular Sequence Data, Molecular Weight, NADP, Protein Binding, RNA, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, zeta-Crystallins},
	pages = {1419--1427}
}

@article{camacho_blast+:_2009,
	title = {{BLAST}+: architecture and applications},
	volume = {10},
	copyright = {2009 Camacho et al; licensee BioMed Central Ltd.},
	issn = {1471-2105},
	shorttitle = {{BLAST}+},
	doi = {10.1186/1471-2105-10-421},
	abstract = {Sequence similarity searching is a very important bioinformatics task. While Basic Local Alignment Search Tool (BLAST) outperforms exact methods through its use of heuristics, the speed of the current BLAST software is suboptimal for very long queries or database sequences. There are also some shortcomings in the user-interface of the current command-line applications.
PMID: 20003500},
	language = {en},
	number = {1},
	urldate = {2014-12-16},
	journal = {BMC Bioinformatics},
	author = {Camacho, Christiam and Coulouris, George and Avagyan, Vahram and Ma, Ning and Papadopoulos, Jason and Bealer, Kevin and Madden, Thomas L.},
	month = dec,
	year = {2009},
	pmid = {20003500},
	pages = {421}
}

@article{koch_human_2003,
	title = {Human {VAT}-1: a calcium-regulated activation marker of human epithelial cells},
	volume = {295},
	issn = {0340-3696, 1432-069X},
	shorttitle = {Human {VAT}-1},
	doi = {10.1007/s00403-003-0421-8},
	abstract = {Background and aims Human VAT-1 (hVAT-1) is a homologue of the synaptic vesicle membrane protein of Torpedo californica. Its coding gene is located near the BRCA1 locus and thus hVAT-1 may be linked to an inherited predisposition to breast and ovary cancer. However, the hVAT-1 protein expression pattern in normal epithelial tissues such as skin, mammary gland and ovary, as well as in tumours of the mammary gland and ovary, has not been studied. Methods To address this issue, an immunohistological analysis of biopsies of normal epidermis and lesional epidermis of bullous pemphigoid and pemphigus vulgaris patients was undertaken. Results hVAT-1-expression was observed in basal keratinocytes of lesional epidermis of bullous pemphigoid patients but not in normal epidermis or in lesional epidermis of pemphigus vulgaris patients. Moreover, hVAT-1 expression in HaCaT cells was found to be calcium-dependent. Normal and malignant mammary and ovary epithelium were found to be hVAT-1-negative. Conclusions Our results indicate that hVAT-1 exerts a specific function in keratinocyte physiology, in particular in calcium-regulated processes, with no evident deregulation in malignancies of the breast and ovary.},
	language = {en},
	number = {5},
	urldate = {2013-08-26},
	journal = {Arch Dermatol Res},
	author = {Koch, Judith and Foekens, John and Timmermans, Mieke and Fink, Wolfram and Wirzbach, Alexander and Kramer, Michael D. and Schaefer, Birgit M.},
	month = sep,
	year = {2003},
	keywords = {Breast cancer, Bullous pemphigoid, Keratinocyte activation, Ovary cancer, Pemphigus vulgaris, VAT-1},
	pages = {203--210},
	file = {Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/9HQPK333/Koch et al. - 2003 - Human VAT-1 a calcium-regulated activation marker.pdf:application/pdf;Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/EU4FFFR3/10.html:text/html}
}

@article{szalai_organization_2002,
	title = {Organization of sex functional mouse alcohol dehydrogenase genes on two overlapping bacterial artificial chromosomes},
	volume = {269},
	journal = {Eur J Biochem},
	author = {Szalai, Gabor and Duester, Greg and Friedman, Robert and Jia, Hongui and Lin, ShaoPing and Roe, Bruce A and Felder, Michael R},
	year = {2002},
	pages = {224--32}
}

@article{reiterer_day_2014,
	title = {Day of the dead: pseudokinases and pseudophosphatases in physiology and disease},
	volume = {24},
	issn = {0962-8924},
	shorttitle = {Day of the dead},
	doi = {10.1016/j.tcb.2014.03.008},
	abstract = {Pseudophosphatases and pseudokinases are increasingly viewed as integral elements of signaling pathways, and there is mounting evidence that they have frequently retained the ability to interact with cellular ‘substrates’, and can exert important roles in different diseases. However, these pseudoenzymes have traditionally received scant attention compared to classical kinases and phosphatases. In this review we explore new findings in the emerging pseudokinase and pseudophosphatase fields, and discuss their different modes of action which include exciting new roles as scaffolds, anchors, spatial modulators, traps, and ligand-driven regulators of canonical kinases and phosphatases. Thus, it is now apparent that pseudokinases and pseudophosphatases both support and drive a panoply of signaling networks. Finally, we highlight recent evidence on their involvement in human pathologies, marking them as potential novel drug targets.},
	number = {9},
	urldate = {2015-04-29},
	journal = {Trends Cell Biol.},
	author = {Reiterer, Veronika and Eyers, Patrick A. and Farhan, Hesso},
	month = sep,
	year = {2014},
	keywords = {ATP, cancer, enzyme, kinase, phosphatase, pseudokinase, pseudophosphatase, signaling, substrate},
	pages = {489--505}
}

@article{wheeler_skylign:_2014,
	title = {Skylign: a tool for creating informative, interactive logos representing sequence alignments and profile hidden {Markov} models},
	volume = {15},
	issn = {1471-2105},
	shorttitle = {Skylign},
	doi = {10.1186/1471-2105-15-7},
	abstract = {Logos are commonly used in molecular biology to provide a compact graphical representation of the conservation pattern of a set of sequences. They render the information contained in sequence alignments or profile hidden Markov models by drawing a stack of letters for each position, where the height of the stack corresponds to the conservation at that position, and the height of each letter within a stack depends on the frequency of that letter at that position.},
	urldate = {2017-02-09},
	journal = {BMC Bioinformatics},
	author = {Wheeler, Travis J. and Clements, Jody and Finn, Robert D.},
	year = {2014},
	keywords = {Alignment logo, Hmm logo, Logo server, Profile logo, Sequence logo, Web logo},
	pages = {7},
	file = {Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/B7DQ4RGV/Wheeler et al. - 2014 - Skylign a tool for creating informative, interact.pdf:application/pdf;Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/KWH69DVP/Wheeler et al. - 2014 - Skylign a tool for creating informative, interact.html:text/html}
}

@article{larkin_clustal_2007,
	title = {Clustal {W} and {Clustal} {X} version 2.0},
	volume = {23},
	number = {21},
	journal = {Bioinformatics},
	author = {Larkin, M A and Blackshields, G and Brown, N P and Chenna, R and McGettigan, P A and McWilliam, H and Valentin, F and Wallace, I M and Wilm, A and Thompson, Julie D and Gibson, Toby J and Higgins, Desmond G},
	year = {2007},
	pages = {2947}
}

@article{duester_recommended_1999,
	title = {Recommended nomenclature for the vertebrate alcohol dehydrogenase gene family},
	volume = {58},
	issn = {0006-2952},
	doi = {10.1016/S0006-2952(99)00065-9},
	abstract = {The alcohol dehydrogenase (ADH) gene family encodes enzymes that metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. Studies on 19 vertebrate animals have identified ADH orthologs across several species, and this has now led to questions of how best to name ADH proteins and genes. Seven distinct classes of vertebrate ADH encoded by non-orthologous genes have been defined based upon sequence homology as well as unique catalytic properties or gene expression patterns. Each class of vertebrate ADH shares \<70\% sequence identity with other classes of ADH in the same species. Classes may be further divided into multiple closely related isoenzymes sharing \>80\% sequence identity such as the case for class I ADH where humans have three class I ADH genes, horses have two, and mice have only one. Presented here is a nomenclature that uses the widely accepted vertebrate ADH class system as its basis. It follows the guidelines of human and mouse gene nomenclature committees, which recommend coordinating names across species boundaries and eliminating Roman numerals and Greek symbols. We recommend that enzyme subunits be referred to by the symbol “ADH” (alcohol dehydrogenase) followed by an Arabic number denoting the class; i.e. ADH1 for class I ADH. For genes we recommend the italicized root symbol “ADH” for human and “Adh” for mouse, followed by the appropriate Arabic number for the class; i.e. ADH1 or Adh1 for class I ADH genes. For organisms where multiple species-specific isoenzymes exist within a class, we recommend adding a capital letter after the Arabic number; i.e. ADH1A, ADH1B, and ADH1C for human $\alpha$, $\beta$, and $\gamma$ class I ADHs, respectively. This nomenclature will accommodate newly discovered members of the vertebrate ADH family, and will facilitate functional and evolutionary studies.},
	number = {3},
	urldate = {2013-08-26},
	journal = {Biochem. Pharmacol.},
	author = {Duester, Gregg and Farrés, Jaume and Felder, Michael R and Holmes, Roger S and Höög, Jan-Olov and Parés, Xavier and Plapp, Bryce V and Yin, Shih-Jiun and Jörnvall, Hans},
	month = aug,
	year = {1999},
	keywords = {Alcohol Dehydrogenase, nomenclature, vertebrate},
	pages = {389--395},
	file = {ScienceDirect Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/N53HSB3I/Duester et al. - 1999 - Recommended nomenclature for the vertebrate alcoho.pdf:application/pdf;ScienceDirect Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/Q8KSGJHG/S0006295299000659.html:text/html}
}

@article{sanghani_structure-function_2006,
	title = {Structure-function relationships in human glutathione-dependent formaldehyde dehydrogenase. {Role} of {Glu}-67 and {Arg}-368 in the catalytic mechanism},
	volume = {45},
	issn = {0006-2960},
	doi = {10.1021/bi052554q},
	abstract = {The active-site zinc in human glutathione-dependent formaldehyde dehydrogenase (FDH) undergoes coenzyme-induced displacement and transient coordination to a highly conserved glutamate residue (Glu-67) during the catalytic cycle. The role of this transient coordination of the active-site zinc to Glu-67 in the FDH catalytic cycle and the associated coenzyme interactions were investigated by studying enzymes in which Glu-67 and Arg-368 were substituted with Leu. Structures of FDH.adenosine 5'-diphosphate ribose (ADP-ribose) and E67L.NAD(H) binary complexes were determined. Steady-state kinetics, isotope effects, and presteady-state analysis of the E67L enzyme show that Glu-67 is critical for capturing the substrates for catalysis. The catalytic efficiency (V/K(m)) of the E67L enzyme in reactions involving S-nitrosoglutathione (GSNO), S-hydroxymethylglutathione (HMGSH) and 12-hydroxydodecanoic acid (12-HDDA) were 25 000-, 3000-, and 180-fold lower, respectively, than for the wild-type enzyme. The large decrease in the efficiency of capturing GSNO and HMGSH by the E67L enzyme results mainly because of the impaired binding of these substrates to the mutant enzyme. In the case of 12-HDDA, a decrease in the rate of hydride transfer is the major factor responsible for the reduction in the efficiency of its capture for catalysis by the E67L enzyme. Binding of the coenzyme is not affected by the Glu-67 substitution. A partial displacement of the active-site zinc in the FDH.ADP-ribose binary complex indicates that the disruption of the interaction between Glu-67 and Arg-368 is involved in the displacement of active-site zinc. Kinetic studies with the R368L enzyme show that the predominant role of Arg-368 is in the binding of the coenzyme. An isomerization of the ternary complex before hydride transfer is detected in the kinetic pathway of HMGSH. Steps involved in the binding of the coenzyme to the FDH active site are also discerned from the unique conformation of the coenzyme in one of the subunits of the E67L.NAD(H) binary complex.},
	language = {eng},
	number = {15},
	journal = {Biochemistry},
	author = {Sanghani, Paresh C. and Davis, Wilhelmina I. and Zhai, LanMin and Robinson, Howard},
	month = apr,
	year = {2006},
	pmid = {16605250},
	keywords = {Adenosine Diphosphate Ribose, Aldehyde Oxidoreductases, Amino Acid Substitution, Arginine, Catalysis, Glutamic Acid, Glutathione, Humans, Hydrogen-Ion Concentration, Kinetics, Lauric Acids, Leucine, Models, Molecular, Protein Conformation, S-nitrosoglutathione, Structure-Activity Relationship, Time Factors, Zinc},
	pages = {4819--4830}
}

@phdthesis{hellgren_enzymatic_2009,
	address = {Stockholm, Sweden},
	type = {Dissertation},
	title = {Enzymatic {Studies} of {Alcohol} {Dehydrogenase} by a {Combination} of {In} {Vitro} and {In} {Silico} {Methods}},
	school = {Karolinska Institutet},
	author = {Hellgren, Mikko},
	year = {2009}
}

@article{lipman_rapid_1985,
	title = {Rapid and sensitive protein similarity searches},
	volume = {227},
	issn = {0036-8075},
	abstract = {An algorithm was developed which facilitates the search for similarities between newly determined amino acid sequences and sequences already available in databases. Because of the algorithm's efficiency on many microcomputers, sensitive protein database searches may now become a routine procedure for molecular biologists. The method efficiently identifies regions of similar sequence and then scores the aligned identical and differing residues in those regions by means of an amino acid replacability matrix. This matrix increases sensitivity by giving high scores to those amino acid replacements which occur frequently in evolution. The algorithm has been implemented in a computer program designed to search protein databases very rapidly. For example, comparison of a 200-amino-acid sequence to the 500,000 residues in the National Biomedical Research Foundation library would take less than 2 minutes on a minicomputer, and less than 10 minutes on a microcomputer (IBM PC).},
	language = {eng},
	number = {4693},
	journal = {Science},
	author = {Lipman, D. J. and Pearson, W. R.},
	month = mar,
	year = {1985},
	pmid = {2983426},
	keywords = {Amino Acid Sequence, Angiotensinogen, Animals, Biological Evolution, Bunyaviridae, Cattle, Computers, Cyclic AMP, Cytochrome c Group, Humans, Information Systems, Microcomputers, Nucleoproteins, Probability, Protein Kinases, Protein Precursors, Proteins, Rats, Software, Viral Proteins},
	pages = {1435--1441}
}

@book{noauthor_molsoft_2012-1,
	title = {Molsoft {L}.{L}.{C}.: {Molsoft}'s {Technology}},
	year = {2012}
}

@article{robins_molecular_2006,
	title = {Molecular model of human {CYP}21 based on mammalian {CYP}2C5: structural features correlate with clinical severity of mutations causing congenital adrenal hyperplasia.},
	volume = {20},
	doi = {10.1210/me.2006-0172},
	abstract = {Enhanced understanding of structure-function relationships of human 21-hydroxylase, CYP21, is required to better understand the molecular causes of congenital adrenal hyperplasia. To this end, a structural model of human CYP21 was calculated based on the crystal structure of rabbit CYP2C5. All but two known allelic variants of missense type, a total of 60 disease-causing mutations and six normal variants, were analyzed using this model. A structural explanation for the corresponding phenotype was found for all but two mutants for which available clinical data are also discrepant with in vitro enzyme activity. Calculations of protein stability of modeled mutants were found to correlate inversely with the corresponding clinical severity. Putative structurally important residues were identified to be involved in heme and substrate binding, redox partner interaction, and enzyme catalysis using docking calculations and analysis of structurally determined homologous cytochrome P450s (CYPs). Functional and structural consequences of seven novel mutations, V139E, C147R, R233G, T295N, L308F, R366C, and M473I, detected in Scandinavian patients with suspected congenital adrenal hyperplasia of different severity, were predicted using molecular modeling. Structural features deduced from the models are in good correlation with clinical severity of CYP21 mutants, which shows the applicability of a modeling approach in assessment of new CYP21 mutations.},
	number = {11},
	journal = {Mol. Endocrinol.},
	author = {Robins, Tiina and Carlsson, Jonas and Sunnerhagen, Maria and Wedell, Anna and Persson, Bengt},
	month = nov,
	year = {2006},
	pages = {2946--64}
}

@book{dayhoff_atlas_1969,
	address = {Silver Spring [Md.]},
	title = {Atlas of protein sequence and structure},
	volume = {1},
	language = {English},
	publisher = {National Biomedical Research Foundation},
	author = {Dayhoff, Margaret Oakley and {National Biomedical Research Foundation}},
	year = {1969},
	note = {OCLC: 605459794}
}

@article{hess_lincs:_1997,
	title = {{LINCS}: {A} {Linear} {Constraint} {Solver} for {Molecular} {Simulations}},
	volume = {18},
	journal = {J. Comp. Chem.},
	author = {Hess, Berk and Bekker, Henk and Berendsen, Herman J C and Fraaije, Johannes G E M},
	year = {1997},
	pages = {1463--1472}
}

@article{jornvall_horse_1970-1,
	title = {Horse liver alcohol dehydrogenase. {The} primary structure of the protein chain of the ethanol-active isoenzyme},
	volume = {16},
	issn = {0014-2956},
	language = {eng},
	number = {1},
	journal = {Eur. J. Biochem.},
	author = {Jörnvall, H.},
	month = sep,
	year = {1970},
	pmid = {4917230},
	keywords = {Alcohol Oxidoreductases, Alkylation, Amino Acid Sequence, Animals, Carbon Isotopes, Chemical Phenomena, Chemistry, Chromatography, Gel, Chymotrypsin, Cyanides, Cysteine, Ethanol, Histidine, Horses, Iodoacetates, Isoenzymes, Liver, Malates, Methionine, Mutation, Pepsin A, Peptides, Serine, Trypsin},
	pages = {25--40}
}

@article{persson_super-family_1994,
	title = {A super-family of medium-chain dehydrogenases/reductases ({MDR}). {Sub}-lines including zeta-crystallin, alcohol and polyol dehydrogenases, quinone oxidoreductase enoyl reductases, {VAT}-1 and other proteins},
	volume = {226},
	issn = {0014-2956},
	abstract = {The protein super-family of medium-chain alcohol dehydrogenases (and glutathione-dependent formaldehyde dehydrogenase), polyol dehydrogenases, threonine dehydrogenase, archaeon glucose dehydrogenase, and eye lens reductase-active zeta-crystallins also includes Escherichia coli quinone oxidoreductase, Torpedo VAT-1 protein, and enoyl reductases of mammalian fatty acid and yeast erythronolide synthases. In addition, two proteins with hitherto unknown function are shown to belong to this super-family of medium-chain dehydrogenases and reductases (MDR). Alignment of zeta-crystallins/quinone oxidoreductases/VAT-1 reveals 38 strictly conserved residues, of which approximately half are glycine residues, including those at several space-restricted turn positions and critical coenzyme-binding positions in the alcohol dehydrogenases. This indicates a conserved three-dimensional structure at the corresponding parts of these distantly related proteins and a conserved binding of a coenzyme in the two proteins with hitherto unknown function, thus ascribing a likely oxidoreductase function to these proteins. When all forms are aligned, including enoyl reductases, a zeta-crystallin homologue from Leishmania and the two proteins with hitherto unknown function, only three residues are strictly conserved among the 106 proteins characterised within the superfamily, and significantly these residues are all glycines, corresponding to Gly66, Gly86 and Gly201 of mammalian class I alcohol dehydrogenase. Notably, these residues are located in different domains. Hence, a distant origin and divergent functions, but related forms and interactions, appear to apply to the entire chains of the many prokaryotic and eukaryotic members. Additionally, in the zeta-crystallins/quinone oxidoreductases, a highly conserved tyrosine residue is found. This residue, in the three-dimensional structure of the homologous alcohol dehydrogenase, is positioned at the subunit cleft that contains the active site and could therefore be involved in catalysis. If so, this residue and its role may resemble the pattern of a conserved tyrosine residue in the different family of short-chain dehydrogenases/reductases (SDR).},
	language = {eng},
	number = {1},
	journal = {Eur. J. Biochem.},
	author = {Persson, B. and Zigler, J. S. and Jörnvall, H.},
	month = nov,
	year = {1994},
	pmid = {7957243},
	keywords = {Alcohol Dehydrogenase, Amino Acid Sequence, Animals, Biological Evolution, Crystallins, Enoyl-(Acyl-Carrier-Protein) Reductase (NADH), Humans, Membrane Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Oxidoreductases, Phylogeny, Quinone Reductases, Sequence Alignment, Sequence Homology, Amino Acid},
	pages = {15--22}
}

@article{ehrig_monomers_1993,
	title = {Monomers of human beta 1 beta 1 alcohol dehydrogenase exhibit activity that differs from the dimer},
	volume = {268},
	issn = {0021-9258},
	abstract = {A previously unreported enzymatic activity is described for monomers of the beta 1 beta 1 isoenzyme of human alcohol dehydrogenase that were prepared from dimeric enzyme by freeze-thaw in liquid nitrogen. Whereas the dimeric enzyme has optimal activity at low substrate concentrations (2.5 mM ethanol, 50 microM NAD+; "low Km" activity), the monomer has its highest activity at high substrate concentrations (1.5 M ethanol, 2.5 mM NAD+; "high Km" activity). While the activity of the monomer does not appear to be saturated at 1.5 M ethanol, its maximal activity at this high ethanol concentration exceeds the Vmax of the dimer by about 3-fold. The apparent Km of NAD+ with monomers is 270 microM, and no activity could be detected with nicotinamide mononucleotide as cofactor. During gel filtration the high Km activity elutes at a lower apparent molecular weight position than the dimer. The kinetics of monomer-to-dimer reassociation are consistent with a second-order process with a rate constant of 240 M-1 s-1. The reassociation rate is markedly enhanced by the presence of NAD+. During refolding of beta 1 beta 1 following denaturation in 6 M guanidine hydrochloride, an enzyme species with high Km activity and spectral properties similar to the freeze-thaw monomer is observed, indicating that a catalytically active monomer is an intermediate in the refolding pathway. The enzymatic activity of the monomer implies that the intersubunit contacts of beta 1 beta 1 are not crucial in establishing a catalytically competent enzyme. However, the differences in specific activity and Km between monomer and dimer suggest that dimerization may serve to modulate the catalytic properties.},
	language = {eng},
	number = {16},
	journal = {J. Biol. Chem.},
	author = {Ehrig, T. and Muhoberac, B. B. and Brems, D. and Bosron, W. F.},
	month = jun,
	year = {1993},
	pmid = {8505301},
	keywords = {Alcohol Dehydrogenase, Chromatography, Gel, Circular Dichroism, Guanidine, Guanidines, Humans, Isoenzymes, Kinetics, Macromolecular Substances, NAD, Protein Denaturation, Protein Folding, Recombinant Proteins, Spectrometry, Fluorescence},
	pages = {11721--11726}
}

@article{zheng_molecular_1993,
	title = {Molecular basis of the alcohol dehydrogenase-negative deer mouse. {Evidence} for deletion of the gene for class {I} enzyme and identification of a possible new enzyme class},
	volume = {268},
	issn = {0021-9258},
	abstract = {The molecular basis of the alcohol dehydrogenase (ADH)-negative deer mouse (Peromyscus maniculatus) has been investigated. Several classes of mammalian ADHs have been recognized based upon biochemical and structural properties. ADH cDNA clones identified by hybridization to a mouse class I ADH cDNA clone were obtained from a deer mouse ADH-positive liver cDNA library. This cDNA has been identified as being a class I sequence and represents the deer mouse Adh-1 gene. An additional cDNA sequence identified in both the ADH-positive and -negative deer mouse cDNA libraries was identified by weak cross-hybridization to the mouse cDNA. This cDNA encodes an amino acid sequence representing a new class of mammalian ADH, and the deer mouse gene for this ADH is named Adh-2. ADH-negative deer mice do not produce mRNA, that is detected by the Adh-1 cDNA probe. However, both stocks of deer mice produce high levels of Adh-2 mRNA in liver. Southern analysis using an essentially full-length Adh-1 cDNA probe has shown that the Adh-1 gene is deleted in the ADH-negative mice. Biochemical analysis of enzyme activity suggests at least three ADH polypeptides are expressed in different tissues and have somewhat different substrate specificities, as in the mouse.},
	language = {eng},
	number = {33},
	journal = {J. Biol. Chem.},
	author = {Zheng, Y. W. and Bey, M. and Liu, H. and Felder, M. R.},
	month = nov,
	year = {1993},
	pmid = {8227055},
	keywords = {Alcohol Dehydrogenase, Amino Acid Sequence, Animals, Base Sequence, Blotting, Southern, Cloning, Molecular, DNA, Complementary, Gene Deletion, Molecular Sequence Data, Peromyscus, RNA, Messenger, Sequence Homology, Amino Acid},
	pages = {24933--24939}
}

@article{thompson_clustal_1994,
	title = {{CLUSTAL} {W}: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice},
	volume = {22},
	journal = {Nucleic Acids Res.},
	author = {Thompson, Julie D and Higgins, Desmond G and Gibson, Toby J},
	year = {1994},
	pages = {4673--4680}
}

@article{hauser_kclust:_2013,
	title = {{kClust}: fast and sensitive clustering of large protein sequence databases},
	volume = {14},
	copyright = {2013 Hauser et al.; licensee BioMed Central Ltd.},
	issn = {1471-2105},
	shorttitle = {{kClust}},
	doi = {10.1186/1471-2105-14-248},
	abstract = {Fueled by rapid progress in high-throughput sequencing, the size of public sequence databases doubles every two years. Searching the ever larger and more redundant databases is getting increasingly inefficient. Clustering can help to organize sequences into homologous and functionally similar groups and can improve the speed, sensitivity, and readability of homology searches. However, because the clustering time is quadratic in the number of sequences, standard sequence search methods are becoming impracticable.},
	language = {en},
	number = {1},
	urldate = {2013-09-12},
	journal = {BMC Bioinformatics},
	author = {Hauser, Maria and Mayer, Christian E. and Söding, Johannes},
	month = aug,
	year = {2013},
	pmid = {23945046},
	pages = {248},
	file = {Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/KIAQZARH/Hauser et al. - 2013 - kClust fast and sensitive clustering of large pro.pdf:application/pdf;Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/V6BX4CXA/Hauser et al. - 2013 - kClust fast and sensitive clustering of large pro.html:text/html}
}

@article{yasunami_human_1991,
	title = {A human alcohol dehydrogenase gene ({ADH}6) encoding an additional class of isozyme.},
	volume = {88},
	issn = {0027-8424},
	abstract = {The human alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) gene family consists of five known loci (ADH1-ADH5), which have been mapped close together on chromosome 4 (4q21-25). ADH isozymes encoded by these genes are grouped in three distinct classes in terms of their enzymological properties. A moderate structural similarity is observed between the members of different classes. We isolated an additional member of the ADH gene family by means of cross-hybridization with the ADH2 (class I) cDNA probe. cDNA clones corresponding to this gene were derived from PCR-amplified libraries as well. The coding sequence of a 368-amino-acid-long open reading frame was interrupted by introns into eight exons and spanned approximately 17 kilobases on the genome. The gene contains a glucocorticoid response element at the 5' region. The transcript was detected in the stomach and liver. The deduced amino acid sequence of the open reading frame showed about 60\% positional identity with known human ADHs. This extent of homology is comparable to interclass similarity in the human ADH family. Thus, the newly identified gene, which is designated ADH6, governs the synthesis of an enzyme that belongs to another class of ADHs presumably with a distinct physiological role.},
	number = {17},
	urldate = {2013-08-26},
	journal = {Proc. Natl. Acad. Sci. U. S. A.},
	author = {Yasunami, M and Chen, C S and Yoshida, A},
	month = sep,
	year = {1991},
	pmid = {1881901},
	pmcid = {PMC52351},
	pages = {7610--7614},
	file = {PubMed Central Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/D27K9WX9/Yasunami et al. - 1991 - A human alcohol dehydrogenase gene (ADH6) encoding.pdf:application/pdf}
}

@article{henikoff_amino_1992,
	title = {Amino acid substitution matrices from protein blocks.},
	volume = {89},
	issn = {0027-8424},
	abstract = {Methods for alignment of protein sequences typically measure similarity by using a substitution matrix with scores for all possible exchanges of one amino acid with another. The most widely used matrices are based on the Dayhoff model of evolutionary rates. Using a different approach, we have derived substitution matrices from about 2000 blocks of aligned sequence segments characterizing more than 500 groups of related proteins. This led to marked improvements in alignments and in searches using queries from each of the groups.},
	number = {22},
	urldate = {2017-04-25},
	journal = {Proc Natl Acad Sci U S A},
	author = {Henikoff, S and Henikoff, J G},
	month = nov,
	year = {1992},
	pmid = {1438297},
	pmcid = {PMC50453},
	pages = {10915--10919},
	file = {PubMed Central Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/R4JFENVE/Henikoff and Henikoff - 1992 - Amino acid substitution matrices from protein bloc.pdf:application/pdf}
}

@incollection{berendsen_intermolecular_1981,
	address = {Dordrecht},
	title = {Intermolecular {Forces}},
	publisher = {Reidel},
	author = {Berendsen, H J C and Postma, J P M and van Gunsteren, W F and Hermans, J},
	editor = {Pullman, B},
	year = {1981},
	pages = {331--342}
}

@article{arnold_swiss-model_2006,
	title = {The {SWISS}-{MODEL} workspace: a web-based environment for protein structure homology modelling},
	volume = {22},
	issn = {1367-4803},
	shorttitle = {The {SWISS}-{MODEL} workspace},
	doi = {10.1093/bioinformatics/bti770},
	number = {2},
	urldate = {2017-03-08},
	journal = {Bioinformatics},
	author = {Arnold, Konstantin and Bordoli, Lorenza and Kopp, Jürgen and Schwede, Torsten},
	month = jan,
	year = {2006},
	pages = {195--201},
	file = {Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/Q5TUGE7E/Arnold et al. - 2006 - The SWISS-MODEL workspace a web-based environment.pdf:application/pdf;Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/JZMGDNNI/The-SWISS-MODEL-workspace-a-web-based-environment.html:text/html}
}

@article{biocca_functional_2009,
	title = {Functional analysis and molecular dynamics simulation of {LOX}-1 {K}167N polymorphism reveal alteration of receptor activity},
	volume = {4},
	journal = {PLoS One},
	author = {Biocca, S. and Falconi, M. and Filesi, I. and Baldini, F. and Vecchione, L. and Mango, R. and Romeo, F. and Federici, G. and Desideri, A. and Novelli, G.},
	year = {2009},
	pages = {e4648}
}

@article{yang_synonymous_1998,
	title = {Synonymous and nonsynonymous rate variation in nuclear genes of mammals},
	volume = {46},
	issn = {0022-2844},
	abstract = {A maximum likelihood approach was used to estimate the synonymous and nonsynonymous substitution rates in 48 nuclear genes from primates, artiodactyls, and rodents. A codon-substitution model was assumed, which accounts for the genetic code structure, transition/transversion bias, and base frequency biases at codon positions. Likelihood ratio tests were applied to test the constancy of nonsynonymous to synonymous rate ratios among branches (evolutionary lineages). It is found that at 22 of the 48 nuclear loci examined, the nonsynonymous/synonymous rate ratio varies significantly across branches of the tree. The result provides strong evidence against a strictly neutral model of molecular evolution. Our likelihood estimates of synonymous and nonsynonymous rates differ considerably from previous results obtained from approximate pairwise sequence comparisons. The differences between the methods are explored by detailed analyses of data from several genes. Transition/transversion rate bias and codon frequency biases are found to have significant effects on the estimation of synonymous and nonsynonymous rates, and approximate methods do not adequately account for those factors. The likelihood approach is preferable, even for pairwise sequence comparison, because more realistic models about the mutation and substitution processes can be incorporated in the analysis.},
	language = {eng},
	number = {4},
	journal = {J. Mol. Evol.},
	author = {Yang, Z. and Nielsen, R.},
	month = apr,
	year = {1998},
	pmid = {9541535},
	keywords = {Animals, Artiodactyla, Cell Nucleus, Evolution, Molecular, Genes, Genetic Variation, Likelihood Functions, Mammals, Models, Genetic, Phylogeny, Primates, Rodentia, Time Factors},
	pages = {409--418}
}

@article{gibbons_structure_2004,
	title = {Structure of three class {I} human alcohol dehydrogenases complexed with isoenzyme specific formamide inhibitors},
	volume = {43},
	issn = {0006-2960},
	doi = {10.1021/bi0489107},
	abstract = {Formamides are aldehyde analogues that have demonstrated potent and selective inhibition of human alcohol dehydrogenase isoenzymes. The alphaalpha, beta(1)beta(1), gamma(2)gamma(2), and sigmasigma isoforms have all been found to be strongly inhibited by substituted formamides. In this paper, the structure of the alphaalpha isoform of human alcohol dehydrogenase complexed with N-cyclopentyl-N-cyclobutylformamide was determined by X-ray crystallography to 2.5 A resolution, the beta(1)beta(1) isoform of human alcohol dehydrogenase complexed with N-benzylformamide and with N-heptylformamide was determined to 1.6 and 1.65 A resolution, respectively, and the structure of the gamma(2)gamma(2) isoform complexed with N-1-methylheptylformamide was determined to 1.45 A resolution. These structures provide the first substrate-level view of the local structural differences that give rise to the individual substrate preferences shown by these highly related isoenzymes. Consistent with previous work, the carbonyl oxygen of the inhibitors interacts directly with the catalytic zinc and the hydroxyl group of Thr48 (Ser48 for gamma(2)gamma(2)) of the enzyme. The benzene ring of N-benzylformamide and the carbon chains of N-heptylformamide and N-1-methylheptylformamide interact with the sides of the hydrophobic substrate pocket whose size and shape is dictated by residue exchanges between the beta(1)beta(1) and gamma(2)gamma(2) isoenzymes. In particular, the exchange of Ser for Thr at position 48 and the exchange of Val for Leu at position 141 in the gamma(2)gamma(2) isoenzyme create an environment with stereoselectivity for the R-enantiomer of the branched N-1-methylheptylformamide inhibitor in this isoenzyme. The primary feature of the alphaalpha isoform is the Ala for Phe93 exchange that enlarges the active site near the catalytic zinc and creates the specificity for the branched N-cyclopentyl-N-cyclobutylformamide inhibitor, which shows the greatest selectivity for this unique isoenzyme of any of the formamide inhibitors.},
	language = {eng},
	number = {39},
	journal = {Biochemistry},
	author = {Gibbons, Brian J. and Hurley, Thomas D.},
	month = oct,
	year = {2004},
	pmid = {15449945},
	keywords = {Alcohol Dehydrogenase, Amino Acid Substitution, Binding Sites, Catalysis, Crystallization, Crystallography, X-Ray, Dimerization, Formamides, Humans, Isoenzymes, Protein Structure, Secondary, Substrate Specificity},
	pages = {12555--12562}
}

@article{guindon_new_2010,
	title = {New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of {PhyML} 3.0},
	volume = {59},
	issn = {1076-836X},
	shorttitle = {New algorithms and methods to estimate maximum-likelihood phylogenies},
	doi = {10.1093/sysbio/syq010},
	abstract = {PhyML is a phylogeny software based on the maximum-likelihood principle. Early PhyML versions used a fast algorithm performing nearest neighbor interchanges to improve a reasonable starting tree topology. Since the original publication (Guindon S., Gascuel O. 2003. A simple, fast and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst. Biol. 52:696-704), PhyML has been widely used ({\textgreater}2500 citations in ISI Web of Science) because of its simplicity and a fair compromise between accuracy and speed. In the meantime, research around PhyML has continued, and this article describes the new algorithms and methods implemented in the program. First, we introduce a new algorithm to search the tree space with user-defined intensity using subtree pruning and regrafting topological moves. The parsimony criterion is used here to filter out the least promising topology modifications with respect to the likelihood function. The analysis of a large collection of real nucleotide and amino acid data sets of various sizes demonstrates the good performance of this method. Second, we describe a new test to assess the support of the data for internal branches of a phylogeny. This approach extends the recently proposed approximate likelihood-ratio test and relies on a nonparametric, Shimodaira-Hasegawa-like procedure. A detailed analysis of real alignments sheds light on the links between this new approach and the more classical nonparametric bootstrap method. Overall, our tests show that the last version (3.0) of PhyML is fast, accurate, stable, and ready to use. A Web server and binary files are available from http://www.atgc-montpellier.fr/phyml/.},
	language = {eng},
	number = {3},
	journal = {Syst. Biol.},
	author = {Guindon, Stéphane and Dufayard, Jean-François and Lefort, Vincent and Anisimova, Maria and Hordijk, Wim and Gascuel, Olivier},
	month = may,
	year = {2010},
	pmid = {20525638},
	keywords = {Algorithms, Classification, Likelihood Functions, Phylogeny, Software},
	pages = {307--321}
}

@article{corpet_multiple_1988,
	title = {Multiple sequence alignment with hierarchical clustering},
	volume = {16},
	issn = {0305-1048},
	abstract = {An algorithm is presented for the multiple alignment of sequences, either proteins or nucleic acids, that is both accurate and easy to use on microcomputers. The approach is based on the conventional dynamic-programming method of pairwise alignment. Initially, a hierarchical clustering of the sequences is performed using the matrix of the pairwise alignment scores. The closest sequences are aligned creating groups of aligned sequences. Then close groups are aligned until all sequences are aligned in one group. The pairwise alignments included in the multiple alignment form a new matrix that is used to produce a hierarchical clustering. If it is different from the first one, iteration of the process can be performed. The method is illustrated by an example: a global alignment of 39 sequences of cytochrome c.},
	language = {eng},
	number = {22},
	journal = {Nucleic Acids Res.},
	author = {Corpet, F.},
	month = nov,
	year = {1988},
	pmid = {2849754},
	pmcid = {PMC338945},
	keywords = {Algorithms, Amino Acid Sequence, Bacteria, Base Sequence, Cytochrome c Group, Models, Genetic, Multigene Family},
	pages = {10881--10890}
}

@article{eklund_structure_1974,
	title = {The structure of horse liver alcohol dehydrogenase},
	volume = {44},
	number = {2},
	journal = {FEBS Letters},
	author = {Eklund, H and Nordström, B and Zeppezauer, E and Söderlund, G and Ohlsson, I and Boiwe, T and Brändén, CI},
	year = {1974},
	pages = {200--204}
}

@article{sanghani_human_2002,
	title = {Human {Glutathione}-{Dependent} {Formaldehyde} {Dehydrogenase}. {Structural} {Changes} {Associated} with {Ternary} {Complex} {Formation}†},
	volume = {41},
	issn = {0006-2960},
	doi = {10.1021/bi026705q},
	abstract = {Human glutathione-dependent formaldehyde dehydrogenase plays an important role in the metabolism of glutathione adducts such as S-(hydroxymethyl)glutathione and S-nitrosoglutathione. The role of specific active site residues in binding these physiologically important substrates and the structural changes during the catalytic cycle of glutathione-dependent formaldehyde dehydrogenase was examined by determining the crystal structure of a ternary complex with S-(hydroxymethyl)glutathione and the reduced coenzyme to 2.6 Å resolution. The formation of the ternary complex caused the movement of the catalytic domain toward the coenzyme-binding domain. This represents the first observation of domain closure in glutathione-dependent formaldehyde dehydrogenase in response to substrate binding. A water molecule adjacent to the 2?-ribose hydroxyl of NADH suggests that the alcohol proton is relayed to solvent directly from the coenzyme, rather than through the action of the terminal histidine residue as observed in the proton relay system for class I alcohol dehydrogenases. S-(Hydroxymethyl)glutathione is directly coordinated to the active site zinc and forms interactions with the highly conserved residues Arg114, Asp55, Glu57, and Thr46. The active site zinc has a tetrahedral coordination environment with Cys44, His66, and Cys173 as the three protein ligands in addition to S-(hydroxymethyl)glutathione. This is in contrast to zinc coordination in the binary coenzyme complex where all of the ligands were contributed by the enzyme and included Glu67 as the fourth protein ligand. This change in zinc coordination is accomplished by an ?2.3 Å movement of the catalytic zinc.},
	number = {51},
	urldate = {2015-04-29},
	journal = {Biochemistry},
	author = {Sanghani, Paresh C. and Bosron, William F. and Hurley, Thomas D.},
	month = dec,
	year = {2002},
	pages = {15189--15194}
}

@article{nilsson_prediction_2002,
	title = {Prediction of partial membrane topologies using a consensus approach},
	volume = {11},
	journal = {Protein Sci.},
	author = {Nilsson, J. and Persson, B. and von Heijne, G},
	year = {2002},
	pages = {2974--2980}
}

@article{smith_identification_1981,
	title = {Identification of common molecular subsequences},
	volume = {147},
	issn = {0022-2836},
	language = {eng},
	number = {1},
	journal = {J. Mol. Biol.},
	author = {Smith, T. F. and Waterman, M. S.},
	month = mar,
	year = {1981},
	pmid = {7265238},
	keywords = {Base Sequence, Models, Chemical},
	pages = {195--197}
}

@article{sievers_fast_2011,
	title = {Fast, scalable generation of high-quality protein multiple sequence alignments using {Clustal} {Omega}},
	volume = {7},
	copyright = {Copyright © 2011 EMBO and Macmillan Publishers Limited. This is an open‐access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.},
	issn = {1744-4292, 1744-4292},
	doi = {10.1038/msb.2011.75},
	abstract = {Multiple sequence alignments are fundamental to many sequence analysis methods. Most alignments are computed using the progressive alignment heuristic. These methods are starting to become a bottleneck in some analysis pipelines when faced with data sets of the size of many thousands of sequences. Some methods allow computation of larger data sets while sacrificing quality, and others produce high‐quality alignments, but scale badly with the number of sequences. In this paper, we describe a new program called Clustal Omega, which can align virtually any number of protein sequences quickly and that delivers accurate alignments. The accuracy of the package on smaller test cases is similar to that of the high‐quality aligners. On larger data sets, Clustal Omega outperforms other packages in terms of execution time and quality. Clustal Omega also has powerful features for adding sequences to and exploiting information in existing alignments, making use of the vast amount of precomputed information in public databases like Pfam.},
	language = {en},
	number = {1},
	urldate = {2017-03-06},
	journal = {Molecular Systems Biology},
	author = {Sievers, Fabian and Wilm, Andreas and Dineen, David and Gibson, Toby J. and Karplus, Kevin and Li, Weizhong and Lopez, Rodrigo and McWilliam, Hamish and Remmert, Michael and Söding, Johannes and Thompson, Julie D. and Higgins, Desmond G.},
	month = jan,
	year = {2011},
	pmid = {21988835},
	keywords = {bioinformatics, Hidden Markov models, multiple sequence alignment},
	pages = {539},
	file = {Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/SGJD9ZKW/Sievers et al. - 2011 - Fast, scalable generation of high‐quality protein .pdf:application/pdf;Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/ZU7FCWVM/539.html:text/html}
}

@article{joosten_series_2011,
	title = {A series of {PDB} related databases for everyday needs},
	volume = {39(Database issue)},
	doi = {10.1093/nar/gkq1105},
	journal = {Nucl. Acids Res.},
	author = {Joosten, Robbie P. and te Beek, Tim A.H. and Krieger, Elmar and Hekkelman, Maarten L. and Hooft, Rob W.W. and Schneider, Reinhard and Sander, Chris and Vriend, Gert},
	month = jan,
	year = {2011},
	pages = {D411--D419}
}

@article{zhang_i-tasser:_2009,
	title = {I-{TASSER}: {Fully} automated protein structure prediction in {CASP}8},
	volume = {77},
	number = {S9},
	journal = {Proteins: Structure, Function, and Bioinformatics},
	author = {Zhang, Yang},
	year = {2009},
	pages = {100--13}
}

@article{ghosh_refined_1994,
	title = {The refined three-dimensional structure of 3 alpha,20 beta-hydroxysteroid dehydrogenase and possible roles of the residues conserved in short-chain dehydrogenases},
	volume = {2},
	issn = {0969-2126},
	abstract = {BACKGROUND: Bacterial 3 alpha,20 beta-hydroxysteroid dehydrogenase reversibly oxidizes the 3 alpha and 20 beta hydroxyl groups of steroids derived from androstanes and pregnanes. It was the first short-chain dehydrogenase to be studied by X-ray crystallography. The previous description of the structure of this enzyme, at 2.6 A resolution, did not permit unambiguous assignment of several important groups. We have further refined the structure of the complex of the enzyme with its cofactor, nicotinamide adenine dinucleotide (NAD), and solvent molecules, at the same resolution.
RESULTS: The asymmetric unit of the crystal contains four monomers, each with 253 amino acid residues, 38 water molecules, and 176 cofactor atoms belonging to four NAD molecules--one for each subunit. The positioning of the cofactor molecule has been modified from our previous model and is deeper in the catalytic cavity as observed for other members of both the long-chain and short-chain dehydrogenase families. The nicotinamide-ribose end of the cofactor has several possible conformations or is dynamically disordered.
CONCLUSIONS: The catalytic site contains residues Tyr152 and Lys156. These two amino acids are strictly conserved in the short-chain dehydrogenase superfamily. Modeling studies with a cortisone molecule in the catalytic site suggest that the Tyr152, Lys156 and Ser139 side chains promote electrophilic attack on the (C20-O) carbonyl oxygen atom, thus enabling the carbon atom to accept a hydride from the reduced cofactor.},
	language = {eng},
	number = {7},
	journal = {Structure},
	author = {Ghosh, D. and Wawrzak, Z. and Weeks, C. M. and Duax, W. L. and Erman, M.},
	month = jul,
	year = {1994},
	pmid = {7922040},
	keywords = {Amino Acid Sequence, Base Sequence, Binding Sites, Cortisone Reductase, Crystallography, X-Ray, Models, Molecular, Molecular Sequence Data, NAD, NADH, NADPH Oxidoreductases, Protein Conformation, Sequence Homology, Amino Acid, Software, Steroids, Streptomyces, Water},
	pages = {629--640}
}

@article{karplus_hidden_1998,
	title = {Hidden {Markov} models for detecting remote protein homologies},
	volume = {14},
	journal = {Bioinformatics},
	author = {Karplus, K and Barrett, C and Hughey, R},
	year = {1998},
	pages = {846--856}
}

@article{jayakumar_human_1995,
	title = {Human fatty acid synthase: properties and molecular cloning},
	volume = {92},
	issn = {0027-8424},
	shorttitle = {Human fatty acid synthase},
	abstract = {Fatty acid synthase (FAS; EC 2.3.1.85) was purified to near homogeneity from a human hepatoma cell line, HepG2. The HepG2 FAS has a specific activity of 600 nmol of NADPH oxidized per min per mg, which is about half that of chicken liver FAS. All the partial activities of human FAS are comparable to those of other animal FASs, except for the beta-ketoacyl synthase, whose significantly lower activity is attributable to the low 4'-phosphopantetheine content of HepG2 FAS. We cloned the human brain FAS cDNA. The cDNA sequence has an open reading frame of 7512 bp that encodes 2504 amino acids (M(r), 272,516). The amino acid sequence of the human FAS has 79\% and 63\% identity, respectively, with the sequences of the rat and chicken enzymes. Northern analysis revealed that human FAS mRNA was about 9.3 kb in size and that its level varied among human tissues, with brain, lung, and liver tissues showing prominent expression. The nucleotide sequence of a segment of the HepG2 FAS cDNA (bases 2327-3964) was identical to that of the cDNA from normal human liver and brain tissues, except for a 53-bp sequence (bases 3892-3944) that does not alter the reading frame. This altered sequence is also present in HepG2 genomic DNA. The origin and significance of this sequence variance in the HepG2 FAS gene are unclear, but the variance apparently does not contribute to the lower activity of HepG2 FAS.},
	language = {eng},
	number = {19},
	journal = {Proc. Natl. Acad. Sci. U.S.A.},
	author = {Jayakumar, A. and Tai, M. H. and Huang, W. Y. and al-Feel, W. and Hsu, M. and Abu-Elheiga, L. and Chirala, S. S. and Wakil, S. J.},
	month = sep,
	year = {1995},
	pmid = {7567999},
	pmcid = {PMC41033},
	keywords = {Amino Acid Sequence, Animals, Base Sequence, Brain, Carcinoma, Hepatocellular, Chickens, Cloning, Molecular, DNA, Complementary, Fatty Acid Synthases, Humans, Liver Neoplasms, Molecular Sequence Data, Pantetheine, Rats, Restriction Mapping, Sequence Analysis, DNA, Sequence Homology, Amino Acid, Species Specificity, Tissue Distribution, Tumor Cells, Cultured},
	pages = {8695--8699}
}

@article{edenberg_comprehensive_1997,
	title = {Comprehensive toxicology},
	volume = {3},
	journal = {Biotransformation},
	author = {Edenberg, HJ and Bosron, WF},
	year = {1997},
	pages = {119--131}
}

@article{eddy_accelerated_2011,
	title = {Accelerated {Profile} {HMM} {Searches}},
	volume = {7},
	issn = {1553-7358},
	doi = {10.1371/journal.pcbi.1002195},
	abstract = {Author Summary Searching sequence databases is one of the most important applications in computational molecular biology. The main workhorse in the field is the BLAST suite of programs. Since the introduction of BLAST in the 1990's, important theoretical advances in homology search methodology have been made using probabilistic inference methods and hidden Markov models (HMMs). However, previous software implementations of these newer probabilistic methods were slower than BLAST by about 100-fold. This hindered their utility, because computation speed is so critical with the rapidly increasing size of modern sequence databases. Here I describe the acceleration methods I implemented in a new, freely available profile HMM software package, HMMER3. HMMER3 makes profile HMM searches about as fast as BLAST, while retaining the power of using probabilistic inference technology.},
	number = {10},
	urldate = {2017-02-01},
	journal = {PLOS Computational Biology},
	author = {Eddy, Sean R.},
	month = oct,
	year = {2011},
	keywords = {BLAST algorithm, Computer software, Database searching, Heuristic alignment procedure, Hidden Markov models, Multiple alignment calculation, Sequence Alignment, Sequence databases},
	pages = {e1002195},
	file = {Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/6AU9EZUI/Eddy - 2011 - Accelerated Profile HMM Searches.pdf:application/pdf;Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/2R3I2MMD/Eddy - 2011 - Accelerated Profile HMM Searches.html:text/html}
}

@article{angebault_recessive_2015,
	title = {Recessive {Mutations} in {RTN}4IP1 {Cause} {Isolated} and {Syndromic} {Optic} {Neuropathies}},
	volume = {97},
	issn = {0002-9297},
	doi = {10.1016/j.ajhg.2015.09.012},
	abstract = {Autosomal-recessive optic neuropathies are rare blinding conditions related to retinal ganglion cell (RGC) and optic-nerve degeneration, for which only mutations in TMEM126A and ACO2 are known. In four families with early-onset recessive optic neuropathy, we identified mutations in RTN4IP1, which encodes a mitochondrial ubiquinol oxydo-reductase. RTN4IP1 is a partner of RTN4 (also known as NOGO), and its ortholog Rad8 in C. elegans is involved in UV light response. Analysis of fibroblasts from affected individuals with a RTN4IP1 mutation showed loss of the altered protein, a deficit of mitochondrial respiratory complex I and IV activities, and increased susceptibility to UV light. Silencing of RTN4IP1 altered the number and morphogenesis of mouse RGC dendrites in vitro and the eye size, neuro-retinal development, and swimming behavior in zebrafish in vivo. Altogether, these data point to a pathophysiological mechanism responsible for RGC early degeneration and optic neuropathy and linking RTN4IP1 functions to mitochondrial physiology, response to UV light, and dendrite growth during eye maturation.},
	number = {5},
	urldate = {2017-01-27},
	journal = {Am J Hum Genet},
	author = {Angebault, Claire and Guichet, Pierre-Olivier and Talmat-Amar, Yasmina and Charif, Majida and Gerber, Sylvie and Fares-Taie, Lucas and Gueguen, Naig and Halloy, François and Moore, David and Amati-Bonneau, Patrizia and Manes, Gael and Hebrard, Maxime and Bocquet, Béatrice and Quiles, Mélanie and Piro-Mégy, Camille and Teigell, Marisa and Delettre, Cécile and Rossel, Mireille and Meunier, Isabelle and Preising, Markus and Lorenz, Birgit and Carelli, Valerio and Chinnery, Patrick F. and Yu-Wai-Man, Patrick and Kaplan, Josseline and Roubertie, Agathe and Barakat, Abdelhamid and Bonneau, Dominique and Reynier, Pascal and Rozet, Jean-Michel and Bomont, Pascale and Hamel, Christian P. and Lenaers, Guy},
	month = nov,
	year = {2015},
	pmid = {26593267},
	pmcid = {PMC4667133},
	pages = {754--760},
	file = {PubMed Central Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/ECNMCP4M/Angebault et al. - 2015 - Recessive Mutations in RTN4IP1 Cause Isolated and .pdf:application/pdf}
}

@article{chou_kinetic_2002,
	title = {Kinetic mechanism of human class {IV} alcohol dehydrogenase functioning as retinol dehydrogenase},
	volume = {277},
	issn = {0021-9258},
	doi = {10.1074/jbc.M201947200},
	abstract = {Molecular genetic studies have indicated that alcohol dehydrogenase may be involved in the synthesis of retinoic acid, a hormonal molecule regulating diverse cellular functions at the transcriptional level. Class IV alcohol dehydrogenase (ADH) has been reported to be the most efficient enzyme catalyzing oxidation of retinol in human ADH family. Initial velocity, product inhibition, and dead-end inhibition experiments were performed with the recombinant human class IV ADH to elucidate kinetic mechanism with all-trans-retinol and all-trans-retinal as natural substrates. Fluorescence quenching was titrated in formation of the binary and abortive ternary enzyme complexes. The minimal mechanism deduced from steady-state kinetic and equilibrium binding studies is best described as an asymmetric rapid equilibrium random mechanism with two dead-end ternary complexes for retinol oxidation and a rapid equilibrium ordered mechanism with one dead-end ternary complex for retinal reduction, a unique mechanistic form for zinc-containing ADHs in the medium chain dehydrogenase/reductase superfamily. Dissociation constants for the binary complexes as well as the productive and abortive ternary complexes determined from different experimental approaches are in reasonable agreement. Kinetic isotope effect studies suggest rate-limiting isomerization of the central ternary complexes in both reaction directions. The potential interference of retinol metabolism by ethanol through the ADH pathway may play a significant role in the pathogenesis of fetal alcohol syndrome and alcohol-related upper digestive tract cancer.},
	language = {eng},
	number = {28},
	journal = {J. Biol. Chem.},
	author = {Chou, Chu-Fang and Lai, Ching-Long and Chang, Yen-Chun and Duester, Gregg and Yin, Shih-Jiun},
	month = jul,
	year = {2002},
	pmid = {11997393},
	keywords = {Alcohol Dehydrogenase, Alcohol Oxidoreductases, Humans, Kinetics, Recombinant Proteins, Signal Transduction, Substrate Specificity},
	pages = {25209--25216}
}

@article{liu_sate-ii:_2012,
	title = {{SATe}-{II}: very fast and accurate simultaneous estimation of multiple sequence alignments and phylogenetic trees},
	volume = {61},
	issn = {1076-836X},
	shorttitle = {{SATe}-{II}},
	doi = {10.1093/sysbio/syr095},
	abstract = {Highly accurate estimation of phylogenetic trees for large data sets is difficult, in part because multiple sequence alignments must be accurate for phylogeny estimation methods to be accurate. Coestimation of alignments and trees has been attempted but currently only SATé estimates reasonably accurate trees and alignments for large data sets in practical time frames (Liu K., Raghavan S., Nelesen S., Linder C.R., Warnow T. 2009b. Rapid and accurate large-scale coestimation of sequence alignments and phylogenetic trees. Science. 324:1561-1564). Here, we present a modification to the original SATé algorithm that improves upon SATé (which we now call SATé-I) in terms of speed and of phylogenetic and alignment accuracy. SATé-II uses a different divide-and-conquer strategy than SATé-I and so produces smaller more closely related subsets than SATé-I; as a result, SATé-II produces more accurate alignments and trees, can analyze larger data sets, and runs more efficiently than SATé-I. Generally, SATé is a metamethod that takes an existing multiple sequence alignment method as an input parameter and boosts the quality of that alignment method. SATé-II-boosted alignment methods are significantly more accurate than their unboosted versions, and trees based upon these improved alignments are more accurate than trees based upon the original alignments. Because SATé-I used maximum likelihood (ML) methods that treat gaps as missing data to estimate trees and because we found a correlation between the quality of tree/alignment pairs and ML scores, we explored the degree to which SATé's performance depends on using ML with gaps treated as missing data to determine the best tree/alignment pair. We present two lines of evidence that using ML with gaps treated as missing data to optimize the alignment and tree produces very poor results. First, we show that the optimization problem where a set of unaligned DNA sequences is given and the output is the tree and alignment of those sequences that maximize likelihood under the Jukes-Cantor model is uninformative in the worst possible sense. For all inputs, all trees optimize the likelihood score. Second, we show that a greedy heuristic that uses GTR+Gamma ML to optimize the alignment and the tree can produce very poor alignments and trees. Therefore, the excellent performance of SATé-II and SATé-I is not because ML is used as an optimization criterion for choosing the best tree/alignment pair but rather due to the particular divide-and-conquer realignment techniques employed.},
	language = {eng},
	number = {1},
	journal = {Syst. Biol.},
	author = {Liu, Kevin and Warnow, Tandy J. and Holder, Mark T. and Nelesen, Serita M. and Yu, Jiaye and Stamatakis, Alexandros P. and Linder, C. Randal},
	month = jan,
	year = {2012},
	pmid = {22139466},
	keywords = {Algorithms, Automation, Computer Simulation, DNA, Evolution, Molecular, Likelihood Functions, Phylogeny, Sequence Alignment, Software},
	pages = {90--106}
}

@article{kent_human_2002,
	title = {The {Human} {Genome} {Browser} at {UCSC}},
	volume = {12},
	issn = {1088-9051, 1549-5469},
	doi = {10.1101/gr.229102},
	abstract = {As vertebrate genome sequences near completion and research refocuses to their analysis, the issue of effective genome annotation display becomes critical. A mature web tool for rapid and reliable display of any requested portion of the genome at any scale, together with several dozen aligned annotation tracks, is provided athttp://genome.ucsc.edu. This browser displays assembly contigs and gaps, mRNA and expressed sequence tag alignments, multiple gene predictions, cross-species homologies, single nucleotide polymorphisms, sequence-tagged sites, radiation hybrid data, transposon repeats, and more as a stack of coregistered tracks. Text and sequence-based searches provide quick and precise access to any region of specific interest. Secondary links from individual features lead to sequence details and supplementary off-site databases. One-half of the annotation tracks are computed at the University of California, Santa Cruz from publicly available sequence data; collaborators worldwide provide the rest. Users can stably add their own custom tracks to the browser for educational or research purposes. The conceptual and technical framework of the browser, its underlying MYSQL database, and overall use are described. The web site currently serves over 50,000 pages per day to over 3000 different users.},
	language = {en},
	number = {6},
	urldate = {2017-04-24},
	journal = {Genome Res.},
	author = {Kent, W. James and Sugnet, Charles W. and Furey, Terrence S. and Roskin, Krishna M. and Pringle, Tom H. and Zahler, Alan M. and Haussler, {and} David},
	month = jun,
	year = {2002},
	pmid = {12045153},
	pages = {996--1006},
	file = {Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/6WDPX4VV/Kent et al. - 2002 - The Human Genome Browser at UCSC.pdf:application/pdf;Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/JIMSAWIM/996.html:text/html}
}

@article{uhlen_tissue-based_2015,
	title = {Tissue-based map of the human proteome},
	volume = {347},
	issn = {1095-9203},
	doi = {10.1126/science.1260419},
	abstract = {Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90\% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body.},
	language = {eng},
	number = {6220},
	journal = {Science},
	author = {Uhlén, Mathias and Fagerberg, Linn and Hallström, Björn M. and Lindskog, Cecilia and Oksvold, Per and Mardinoglu, Adil and Sivertsson, Åsa and Kampf, Caroline and Sjöstedt, Evelina and Asplund, Anna and Olsson, IngMarie and Edlund, Karolina and Lundberg, Emma and Navani, Sanjay and Szigyarto, Cristina Al-Khalili and Odeberg, Jacob and Djureinovic, Dijana and Takanen, Jenny Ottosson and Hober, Sophia and Alm, Tove and Edqvist, Per-Henrik and Berling, Holger and Tegel, Hanna and Mulder, Jan and Rockberg, Johan and Nilsson, Peter and Schwenk, Jochen M. and Hamsten, Marica and von Feilitzen, Kalle and Forsberg, Mattias and Persson, Lukas and Johansson, Fredric and Zwahlen, Martin and von Heijne, Gunnar and Nielsen, Jens and Pontén, Fredrik},
	month = jan,
	year = {2015},
	pmid = {25613900},
	keywords = {alternative splicing, Cell Line, Databases, Protein, Female, Genes, Genetic Code, Humans, Internet, Male, Membrane Proteins, Mitochondrial Proteins, Neoplasms, Protein Array Analysis, Protein Isoforms, Proteome, Tissue Distribution, Transcription, Genetic},
	pages = {1260419}
}

@article{karplus_molecular_1990,
	title = {Molecular dynamics simulations in biology},
	volume = {347},
	copyright = {© 1990 Nature Publishing Group},
	doi = {10.1038/347631a0},
	abstract = {Molecular dynamics—the science of simulating the motions of a system of particles—applied to biological macromolecules gives the fluctuations in the relative positions of the atoms in a protein or in DNA as a function of time. Knowledge of these motions provides insights into biological phenomena such as the role of flexibility in ligand binding and the rapid solvation of the electron transfer state in photosynthesis. Molecular dynamics is also being used to determine protein structures from NMR, to refine protein X-ray crystal structures faster from poorer starting models, and to calculate the free energy changes resulting from mutations in proteins.},
	language = {en},
	number = {6294},
	urldate = {2015-04-17},
	journal = {Nature},
	author = {Karplus, Martin and Petsko, Gregory A.},
	month = oct,
	year = {1990},
	pages = {631--639}
}

@article{stromberg_human_2000,
	title = {Human class {V} alcohol dehydrogenase ({ADH}5): {A} complex transcription unit generates {C}-terminal multiplicity},
	volume = {278},
	issn = {0006-291X},
	shorttitle = {Human {Class} {V} {Alcohol} {Dehydrogenase} ({ADH}5)},
	doi = {10.1006/bbrc.2000.3837},
	abstract = {The human ADH5 gene was reported to lack the last exon compared to other mammalian ADHs and consequently should be expressed as a truncated protein. Here we show with PCR amplification of 3′-cDNA ends that the ADH5 gene harbors the “missing” exon. Besides a cDNA identical to the published sequence, we found full-length transcripts that contained additional codons for eight amino acid residues. Northern blot analysis established the full-length variant as the major transcript with the strongest signal from adult liver. Sequence analysis of genomic DNA confirmed that the ADH5 gene displays composite internal/terminal exons, which can be differentially processed; i.e., 3′-end generation is a result of competition between polyadenylation and splicing.},
	number = {3},
	urldate = {2013-08-26},
	journal = {Biochem. Biophys. Res. Commun.},
	author = {Strömberg, Patrik and Höög, Jan-Olov},
	month = nov,
	year = {2000},
	keywords = {alternative splicing, fetal, human alcohol dehydrogenase, mRNA processing, polyadenylation, tissue},
	pages = {544--549},
	file = {ScienceDirect Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/ADIDWVG6/Strömberg and Höög - 2000 - Human Class V Alcohol Dehydrogenase (ADH5) A Comp.pdf:application/pdf;ScienceDirect Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/SCMBV3EU/S0006291X00938373.html:text/html}
}

@misc{bethesda_md:_national_center_for_biotechnology_information_national_library_of_medicine_database_nodate,
	type = {Database},
	title = {Database of {Single} {Nucleotide} {Polymorphisms} ({dbSNP})},
	urldate = {2014-11-13},
	journal = {Reference SNP (refSNP) Cluster Report: rs28720152},
	author = {{Bethesda (MD): National Center for Biotechnology Information, National Library of Medicine}}
}

@article{van_der_spoel_gromacs:_2005,
	title = {{GROMACS}: {Fast}, {Flexible} and {Free}},
	volume = {26},
	number = {16},
	journal = {J. Comput. Chem.},
	author = {van der Spoel, David and Lindahl, Erik and Hess, Berk and Groenhof, Gerrit and Mark, Alan E. and Berendsen, Herman J. C.},
	year = {2005},
	pages = {1701--18}
}

@article{lassmann_kalign--accurate_2005,
	title = {Kalign--an accurate and fast multiple sequence alignment algorithm},
	volume = {6},
	issn = {1471-2105},
	doi = {10.1186/1471-2105-6-298},
	abstract = {BACKGROUND: The alignment of multiple protein sequences is a fundamental step in the analysis of biological data. It has traditionally been applied to analyzing protein families for conserved motifs, phylogeny, structural properties, and to improve sensitivity in homology searching. The availability of complete genome sequences has increased the demands on multiple sequence alignment (MSA) programs. Current MSA methods suffer from being either too inaccurate or too computationally expensive to be applied effectively in large-scale comparative genomics.
RESULTS: We developed Kalign, a method employing the Wu-Manber string-matching algorithm, to improve both the accuracy and speed of multiple sequence alignment. We compared the speed and accuracy of Kalign to other popular methods using Balibase, Prefab, and a new large test set. Kalign was as accurate as the best other methods on small alignments, but significantly more accurate when aligning large and distantly related sets of sequences. In our comparisons, Kalign was about 10 times faster than ClustalW and, depending on the alignment size, up to 50 times faster than popular iterative methods.
CONCLUSION: Kalign is a fast and robust alignment method. It is especially well suited for the increasingly important task of aligning large numbers of sequences.},
	language = {eng},
	journal = {BMC Bioinformatics},
	author = {Lassmann, Timo and Sonnhammer, Erik L. L.},
	month = dec,
	year = {2005},
	pmid = {16343337},
	pmcid = {PMC1325270},
	keywords = {Algorithms, Databases, Nucleic Acid, Databases, Protein, Genome, Genomics, Reproducibility of Results, Sequence Alignment, Sequence Analysis, DNA, Sequence Analysis, Protein},
	pages = {298}
}

@article{chakraborty_fogsaa:_2013,
	title = {{FOGSAA}: {Fast} {Optimal} {Global} {Sequence} {Alignment} {Algorithm}},
	volume = {3},
	copyright = {© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.},
	issn = {2045-2322},
	shorttitle = {{FOGSAA}},
	doi = {10.1038/srep01746},
	abstract = {In this article we propose a Fast Optimal Global Sequence Alignment Algorithm, FOGSAA, which aligns a pair of nucleotide/protein sequences faster than any optimal global alignment method including the widely used Needleman-Wunsch (NW) algorithm.},
	language = {en},
	urldate = {2017-03-24},
	journal = {Scientific Reports},
	author = {Chakraborty, Angana and Bandyopadhyay, Sanghamitra},
	month = apr,
	year = {2013},
	pages = {1746},
	file = {Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/K8ZXXAGP/srep01746.html:text/html}
}

@article{jackson_dead_2015,
	title = {Dead enzymes in the aldehyde dehydrogenase gene family: role in drug metabolism and toxicology},
	volume = {11},
	issn = {1742-5255},
	shorttitle = {Dead enzymes in the aldehyde dehydrogenase gene family},
	doi = {10.1517/17425255.2016.1108406},
	abstract = {Introduction: Dead enzymes are gene products (proteins) that lack key residues required for catalytic activity. In the pre-genome era, dead enzymes were thought to occur only rarely. However, they now have been shown to represent upwards of 10\% of the total enzyme population in many families. The aldehyde dehydrogenase (ALDH) gene family encodes proteins that, depending on the isozyme, may be either catalytically-active or -inactive. Importantly, several ALDHs exhibit biological activities independent of their catalytic activity. For many of these, the physiological and pathophysiological functions remain to be established.Areas covered: This article reviews the non-enzymatic functions of the ALDH superfamily. In addition, a search for additional non-catalytic ALDH records is undertaken. Our computational analyses reveal that there are currently 182 protein records (divided into 19 groups) that meet the criteria for dead enzymes.Expert Opinion: Dead enzymes have the potential to exert biological actions through protein-protein interaction and allosteric modulation of the activity of an active enzyme. In addition, a dead enzyme may also influence availability of substrate for other active enzymes by sequestering substrate, and/or anchoring the substrate to a particular subcellular space. A large number of putatively non-catalytic ALDH proteins exist that warrant further study.},
	number = {12},
	urldate = {2015-12-18},
	journal = {Expert Opinion on Drug Metabolism \& Toxicology},
	author = {Jackson, Brian C. and Thompson, David C. and Charkoftaki, Georgia and Vasiliou, Vasilis},
	month = dec,
	year = {2015},
	pmid = {26558415},
	pages = {1839--1847}
}

@book{higgs_bioinformatics_2005,
	address = {Oxford},
	title = {Bioinformatics and {Molecular} {Evolution}},
	publisher = {Blackwell Publishing},
	author = {Higgs, Paul G and Attwood, Teresa K},
	year = {2005}
}

@article{alwine_method_1977,
	title = {Method for detection of specific {RNAs} in agarose gels by transfer to diazobenzyloxymethyl-paper and hybridization with {DNA} probes},
	volume = {74},
	issn = {0027-8424},
	abstract = {We describe a technique for transferring electrophoretically separated bands of RNA from an agarose gel to paper strips. The RNA is coupled covalently to diazobenzyloxymethyl groups on the paper. After transfer and appropriate treatment of the paper to destroy remaining diazo groups, specific RNA bands can be detected by hybridization with 32P-labeled DNA probes followed by autoradiography. This procedure allows detection of specific RNA bands with high sensitivity and low background.},
	language = {eng},
	number = {12},
	journal = {Proc. Natl. Acad. Sci. U.S.A.},
	author = {Alwine, J. C. and Kemp, D. J. and Stark, G. R.},
	month = dec,
	year = {1977},
	pmid = {414220},
	pmcid = {PMC431715},
	keywords = {Animals, Autoradiography, Cellulose, Chemical Phenomena, Chemistry, Diazonium Compounds, Drosophila melanogaster, Electrophoresis, Agar Gel, Nucleic Acid Hybridization, RNA, RNA, Ribosomal, Solubility},
	pages = {5350--5354}
}

@article{crick_central_1970,
	title = {Central dogma of molecular biology},
	volume = {227},
	issn = {0028-0836},
	language = {eng},
	number = {5258},
	journal = {Nature},
	author = {Crick, F.},
	month = aug,
	year = {1970},
	pmid = {4913914},
	keywords = {DNA, Genetic Code, History, 20th Century, Molecular Biology, Protein Biosynthesis, Proteins, RNA},
	pages = {561--563}
}

@article{jornvall_alcohol_1981,
	title = {Alcohol and polyol dehydrogenases are both divided into two protein types, and structural properties cross-relate the different enzyme activities within each type.},
	volume = {78},
	issn = {0027-8424},
	abstract = {Sorbitol dehydrogenase from sheep liver shows similarities to mammalian and yeast alcohol dehydrogenases. Comparisons based on peptides from segments of sorbitol dehydrogenase reveal that homologous regions with 38\% identity include two ligands to the active site zinc atom in liver alcohol dehydrogenase, as well as further important residues. Similarities in in other regions are less extensive, exactly as they are between different alcohol dehydrogenases. In all aspects, sorbitol dehydrogenase appears as a typical member of the alcohol dehydrogenase family. On the other hand, alcohol dehydrogenase from Drosophila, which has a shorter subunit, is not closely related to either of these enzymes, except for a region that probably corresponds to the first part of the coenzyme binding domain in many dehydrogenases. Instead, Drosophila alcohol dehydrogenase in its supposed catalytic region shows similarities toward Klebsiella ribitol dehydrogenase, which also has a small subunit. It may be concluded that both alcohol and polyol dehydrogenases show two types of protein subunit, reflecting an early subdivision of polypeptide types into "long" and "short" subunits rather than into different enzymatic specificities or quaternary structures. The relationships explain known properties of all these enzymes and provide insight into functional mechanisms and evolutionary interpretations.},
	number = {7},
	urldate = {2017-04-27},
	journal = {Proc Natl Acad Sci U S A},
	author = {Jörnvall, H and Persson, M and Jeffery, J},
	month = jul,
	year = {1981},
	pmid = {7027257},
	pmcid = {PMC319762},
	pages = {4226--4230},
	file = {PubMed Central Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/E8EKSS4A/Jörnvall et al. - 1981 - Alcohol and polyol dehydrogenases are both divided.pdf:application/pdf}
}

@article{katoh_mafft:_2002,
	title = {{MAFFT}: a novel method for rapid multiple sequence alignment based on fast {Fourier} transform},
	volume = {30},
	number = {14},
	journal = {Nucl. Acids Res.},
	author = {Katoh, Kazutaka and Misawa, Kazuharu and Kuma, Kei‐ichi and Miyata, Takashi},
	year = {2002},
	pages = {3059--3066}
}

@article{the_uniprot_consortium_uniprot:_2015,
	title = {{UniProt}: a hub for protein information},
	volume = {43},
	issn = {0305-1048},
	shorttitle = {{UniProt}},
	doi = {10.1093/nar/gku989},
	abstract = {UniProt is an important collection of protein sequences and their annotations, which has doubled in size to 80 million sequences during the past year. This growth in sequences has prompted an extension of UniProt accession number space from 6 to 10 characters. An increasing fraction of new sequences are identical to a sequence that already exists in the database with the majority of sequences coming from genome sequencing projects. We have created a new proteome identifier that uniquely identifies a particular assembly of a species and strain or subspecies to help users track the provenance of sequences. We present a new website that has been designed using a user-experience design process. We have introduced an annotation score for all entries in UniProt to represent the relative amount of knowledge known about each protein. These scores will be helpful in identifying which proteins are the best characterized and most informative for comparative analysis. All UniProt data is provided freely and is available on the web at http://www.uniprot.org/.},
	number = {Database issue},
	urldate = {2017-03-06},
	journal = {Nucleic Acids Res},
	author = {{The UniProt Consortium}},
	month = jan,
	year = {2015},
	pmid = {25348405},
	pmcid = {PMC4384041},
	pages = {D204--D212}
}

@article{paquet_molecular_2015,
	title = {Molecular {Dynamics}, {Monte} {Carlo} {Simulations}, and {Langevin} {Dynamics}: {A} {Computational} {Review}},
	volume = {2015},
	issn = {2314-6133},
	shorttitle = {Molecular {Dynamics}, {Monte} {Carlo} {Simulations}, and {Langevin} {Dynamics}},
	doi = {10.1155/2015/183918},
	abstract = {Macromolecular structures, such as neuraminidases, hemagglutinins, and monoclonal antibodies, are not rigid entities. Rather, they are characterised by their flexibility, which is the result of the interaction and collective motion of their constituent atoms. This conformational diversity has a significant impact on their physicochemical and biological properties. Among these are their structural stability, the transport of ions through the M2 channel, drug resistance, macromolecular docking, binding energy, and rational epitope design. To assess these properties and to calculate the associated thermodynamical observables, the conformational space must be efficiently sampled and the dynamic of the constituent atoms must be simulated. This paper presents algorithms and techniques that address the abovementioned issues. To this end, a computational review of molecular dynamics, Monte Carlo simulations, Langevin dynamics, and free energy calculation is presented. The exposition is made from first principles to promote a better understanding of the potentialities, limitations, applications, and interrelations of these computational methods.},
	language = {en},
	urldate = {2017-04-02},
	journal = {BioMed Research International},
	author = {Paquet, Eric and Viktor, Herna L.},
	month = feb,
	year = {2015},
	pages = {e183918},
	file = {Full Text PDF:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/U9I4VZK6/Paquet and Viktor - 2015 - Molecular Dynamics, Monte Carlo Simulations, and L.pdf:application/pdf;Snapshot:/home/talavis/.zotero/zotero/etop8sp2.default/zotero/storage/QGFTKIG4/183918.html:application/xhtml+xml}
}