{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T23:41:03Z","timestamp":1778110863345,"version":"3.51.4"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2018,4,5]],"date-time":"2018-04-05T00:00:00Z","timestamp":1522886400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1005756","type":"journal-article","created":{"date-parts":[[2018,4,5]],"date-time":"2018-04-05T19:59:44Z","timestamp":1522958384000},"page":"e1005756","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["New computational approaches to understanding molecular protein function"],"prefix":"10.1371","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0528-2049","authenticated-orcid":true,"given":"Jacquelyn S.","family":"Fetrow","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0375-9015","authenticated-orcid":true,"given":"Patricia C.","family":"Babbitt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2018,4,5]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"M Ashburner","year":"2000","journal-title":"Nat Genet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"9950","DOI":"10.1021\/bi201312u","article-title":"The Enzyme Function Initiative","volume":"50","author":"JA Gerlt","year":"2011","journal-title":"Biochemistry"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"SF Altschul","year":"1990","journal-title":"J Mol Biol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped BLAST and PSI-BLAST: a new generation of protein database search programs","volume":"25","author":"SF Altschul","year":"1997","journal-title":"Nucleic Acids Res"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/978-1-62703-646-7_6","article-title":"Clustal Omega, accurate alignment of very large numbers of sequences","volume":"1079","author":"F Sievers","year":"2014","journal-title":"Methods Mol Biol Clifton NJ"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s13059-016-1037-6","article-title":"An expanded evaluation of protein function prediction methods shows an improvement in accuracy","volume":"17","author":"Y Jiang","year":"2016","journal-title":"Genome Biol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"e1000605","DOI":"10.1371\/journal.pcbi.1000605","article-title":"Annotation error in public databases: misannotation of molecular function in enzyme superfamilies","volume":"5","author":"AM Schnoes","year":"2009","journal-title":"PLoS Comput Biol"},{"key":"ref8","first-page":"bas019","article-title":"The PRINTS database: a fine-grained protein sequence annotation and analysis resource\u2014its status in 2012","volume":"2012","author":"TK Attwood","year":"2012","journal-title":"Database J Biol Databases Curation"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"D161","DOI":"10.1093\/nar\/gkp885","article-title":"PROSITE, a protein domain database for functional characterization and annotation","volume":"38","author":"CJA Sigrist","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1006\/jmbi.1998.1993","article-title":"Method for prediction of protein function from sequence using the sequence-to-structure-to-function paradigm with application to glutaredoxins\/thioredoxins and T1 ribonucleases","volume":"281","author":"JS Fetrow","year":"1998","journal-title":"J Mol Biol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"3341","DOI":"10.1093\/nar\/gkg506","article-title":"Annotation in three dimensions. PINTS: Patterns in Non-homologous Tertiary Structures","volume":"31","author":"A Stark","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"D129","DOI":"10.1093\/nar\/gkh028","article-title":"The Catalytic Site Atlas: a resource of catalytic sites and residues identified in enzymes using structural data","volume":"32","author":"CT Porter","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1093\/bioinformatics\/bts510","article-title":"EFICAz2.5: application of a high-precision enzyme function predictor to 396 proteomes","volume":"28","author":"N Kumar","year":"2012","journal-title":"Bioinforma Oxf Engl"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1093\/nar\/gkp1049","article-title":"GeMMA: functional subfamily classification within superfamilies of predicted protein structural domains","volume":"38","author":"DA Lee","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"e160","DOI":"10.1371\/journal.pcbi.0030160","article-title":"Automated protein subfamily identification and classification","volume":"3","author":"DP Brown","year":"2007","journal-title":"PLoS Comput Biol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1093\/bioinformatics\/btq595","article-title":"Identification of subfamily-specific sites based on active sites modeling and clustering","volume":"26","author":"RC de Melo-Minardi","year":"2010","journal-title":"Bioinforma Oxf Engl"},{"key":"ref17","article-title":"An approach to functionally relevant clustering of the protein universe: Active site profile-based clustering of protein structures and sequences","author":"ST Knutson","year":"2017","journal-title":"Protein Sci Publ Protein Soc"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1093\/bioinformatics\/17.9.853","article-title":"BioLayout\u2014an automatic graph layout algorithm for similarity visualization","volume":"17","author":"AJ Enright","year":"2001","journal-title":"Bioinforma Oxf Engl"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"e4345","DOI":"10.1371\/journal.pone.0004345","article-title":"Using sequence similarity networks for visualization of relationships across diverse protein superfamilies","volume":"4","author":"HJ Atkinson","year":"2009","journal-title":"PLoS ONE"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"PREPRINT0002","DOI":"10.1186\/gb-2002-3-3-preprint0002","article-title":"Using orthologous and paralogous proteins to identify specificity determining residues","volume":"3","author":"LA Mirny","year":"2002","journal-title":"Genome Biol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.jmb.2003.08.057","article-title":"How well is enzyme function conserved as a function of pairwise sequence identity?","volume":"333","author":"W Tian","year":"2003","journal-title":"J Mol Biol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/S0022-2836(02)00016-5","article-title":"Enzyme function less conserved than anticipated","volume":"318","author":"B Rost","year":"2002","journal-title":"J Mol Biol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.jmb.2008.12.045","article-title":"Domain-based and family-specific sequence identity thresholds increase the levels of reliable protein function transfer","volume":"387","author":"S Addou","year":"2009","journal-title":"J Mol Biol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"e1002318","DOI":"10.1371\/journal.pcbi.1002318","article-title":"The FGGY carbohydrate kinase family: insights into the evolution of functional specificities","volume":"7","author":"Y Zhang","year":"2011","journal-title":"PLoS Comput Biol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"e1004926","DOI":"10.1371\/journal.pcbi.1004926","article-title":"Novel Computational Protocols for Functionally Classifying and Characterising Serine Beta-Lactamases","volume":"12","author":"D Lee","year":"2016","journal-title":"PLoS Comput Biol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"D521","DOI":"10.1093\/nar\/gkt1130","article-title":"The Structure-Function Linkage Database","volume":"42","author":"E Akiva","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"R8","DOI":"10.1186\/gb-2006-7-1-r8","article-title":"A gold standard set of mechanistically diverse enzyme superfamilies","volume":"7","author":"SD Brown","year":"2006","journal-title":"Genome Biol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1002\/pro.2724","article-title":"Comparison of topological clustering within protein networks using edge metrics that evaluate full sequence, full structure, and active site microenvironment similarity","volume":"24","author":"JB Leuthaeuser","year":"2015","journal-title":"Protein Sci"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"e1005284","DOI":"10.1371\/journal.pcbi.1005284","article-title":"An Atlas of Peroxiredoxins Created Using an Active Site Profile-Based Approach to Functionally Relevant Clustering of Proteins","volume":"13","author":"AF Harper","year":"2017","journal-title":"PLoS Comput Biol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"W148","DOI":"10.1093\/nar\/gkv488","article-title":"CATH FunFHMMer web server: protein functional annotations using functional family assignments","volume":"43","author":"S Das","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.1093\/bioinformatics\/bts565","article-title":"CD-HIT: accelerated for clustering the next-generation sequencing data","volume":"28","author":"L Fu","year":"2012","journal-title":"Bioinforma Oxf Engl"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"e1005001","DOI":"10.1371\/journal.pcbi.1005001","article-title":"Isofunctional Protein Subfamily Detection Using Data Integration and Spectral Clustering","volume":"12","author":"E Boari de Lima","year":"2016","journal-title":"PLoS Comput Biol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"D279","DOI":"10.1093\/nar\/gkv1344","article-title":"The Pfam protein families database: towards a more sustainable future","volume":"44","author":"RD Finn","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1002\/cbdv.200590125","article-title":"Chemical and structural diversity in cyclooxygenase protein active sites","volume":"2","author":"RG Huff","year":"2005","journal-title":"Chem Biodivers"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.jmb.2003.09.062","article-title":"Structure-based active site profiles for genome analysis and functional family subclassification","volume":"334","author":"SA Cammer","year":"2003","journal-title":"J Mol Biol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"e1003874","DOI":"10.1371\/journal.pcbi.1003874","article-title":"Predicting the functions and specificity of triterpenoid synthases: a mechanism-based multi-intermediate docking approach","volume":"10","author":"B-X Tian","year":"2014","journal-title":"PLoS Comput Biol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"e1005053","DOI":"10.1371\/journal.pcbi.1005053","article-title":"Defining the Product Chemical Space of Monoterpenoid Synthases","volume":"12","author":"B Tian","year":"2016","journal-title":"PLoS Comput Biol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"5661","DOI":"10.1073\/pnas.1505127112","article-title":"Computational-guided discovery and characterization of a sesquiterpene synthase from Streptomyces clavuligerus","volume":"112","author":"J-Y Chow","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"16489","DOI":"10.1021\/bi9616413","article-title":"The enolase superfamily: a general strategy for enzyme-catalyzed abstraction of the alpha-protons of carboxylic acids","volume":"35","author":"PC Babbitt","year":"1996","journal-title":"Biochemistry (Mosc)"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1074\/jbc.R111.240945","article-title":"Divergent evolution in enolase superfamily: strategies for assigning functions","volume":"287","author":"JA Gerlt","year":"2012","journal-title":"J Biol Chem"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.abb.2004.07.034","article-title":"Divergent evolution in the enolase superfamily: the interplay of mechanism and specificity","volume":"433","author":"JA Gerlt","year":"2005","journal-title":"Arch Biochem Biophys"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1002\/prot.22936","article-title":"Analysis of the peroxiredoxin family: using active-site structure and sequence information for global classification and residue analysis","volume":"79","author":"KJ Nelson","year":"2011","journal-title":"Proteins"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"E4148","DOI":"10.1073\/pnas.1406134111","article-title":"Basis for substrate recognition and distinction by matrix metalloproteinases","volume":"111","author":"BI Ratnikov","year":"2014","journal-title":"Proc Natl Acad Sci U S A"}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1005756","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T07:15:42Z","timestamp":1540278942000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1005756"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,5]]},"references-count":43,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2018,4,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1005756","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,5]]}}}