{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T08:39:57Z","timestamp":1778575197205,"version":"3.51.4"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"16","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Polypharmacology (the ability of a single drug to affect multiple targets) is a key feature that may explain part of the decreasing success of conventional drug discovery strategies driven by the quest for drugs to act selectively on a single target. Most drug targets are proteins that are composed of domains (their structural and functional building blocks).<\/jats:p>\n               <jats:p>Results: In this work, we model drug\u2013domain networks to explore the role of protein domains as drug targets and to explain drug polypharmacology in terms of the interactions between drugs and protein domains. We find that drugs are organized around a privileged set of druggable domains.<\/jats:p>\n               <jats:p>Conclusions: Protein domains are a good proxy for drug targets, and drug polypharmacology emerges as a consequence of the multi-domain composition of proteins.<\/jats:p>\n               <jats:p>Contact: \u00a0amoyag@uma.es<\/jats:p>\n               <jats:p>Supplementary information: Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btt321","type":"journal-article","created":{"date-parts":[[2013,6,6]],"date-time":"2013-06-06T00:44:12Z","timestamp":1370479452000},"page":"1934-1937","source":"Crossref","is-referenced-by-count":20,"title":["Insights into polypharmacology from drug-domain associations"],"prefix":"10.1093","volume":"29","author":[{"given":"Aurelio A.","family":"Moya-Garc\u00eda","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of Malaga, 29071 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan A. G.","family":"Ranea","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, University of Malaga, 29071 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,6,5]]},"reference":[{"key":"2023020305200871100_btt321-B1","doi-asserted-by":"crossref","first-page":"D211","DOI":"10.1093\/nar\/gkp985","article-title":"The Pfam protein families database","volume":"38","author":"Finn","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"2023020305200871100_btt321-B2","doi-asserted-by":"crossref","first-page":"8685","DOI":"10.1073\/pnas.0701361104","article-title":"The human disease network","volume":"104","author":"Goh","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023020305200871100_btt321-B3","doi-asserted-by":"crossref","first-page":"bar041","DOI":"10.1093\/database\/bar041","article-title":"BioMart Central Portal: an open database network for the biological community","volume":"2011","author":"Guberman","year":"2011","journal-title":"Database (Oxford)"},{"key":"2023020305200871100_btt321-B4","doi-asserted-by":"crossref","first-page":"D919","DOI":"10.1093\/nar\/gkm862","article-title":"SuperTarget and Matador: resources for exploring drug-target relationships","volume":"36","author":"G\u00fcnther","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2023020305200871100_btt321-B5","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/nrd892","article-title":"The druggable genome","volume":"1","author":"Hopkins","year":"2002","journal-title":"Nat. Rev. Drug. Discov."},{"key":"2023020305200871100_btt321-B6","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nchembio.118","article-title":"Network pharmacology: the next paradigm in drug discovery","volume":"4","author":"Hopkins","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"2023020305200871100_btt321-B7","doi-asserted-by":"crossref","first-page":"D1035","DOI":"10.1093\/nar\/gkq1126","article-title":"DrugBank 3.0: a comprehensive resource for \u2018Omics\u2019 research on drugs","volume":"39","author":"Knox","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"2023020305200871100_btt321-B8","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/nature01256","article-title":"The structure of the protein universe and genome evolution","volume":"420","author":"Koonin","year":"2002","journal-title":"Nature"},{"key":"2023020305200871100_btt321-B9","doi-asserted-by":"crossref","first-page":"e12528","DOI":"10.1371\/journal.pone.0012528","article-title":"Community landscapes: an integrative approach to determine overlapping network module hierarchy, identify key nodes and predict network dynamics","volume":"5","author":"Kov\u00e1cs","year":"2010","journal-title":"PLoS One"},{"key":"2023020305200871100_btt321-B10","doi-asserted-by":"crossref","first-page":"D684","DOI":"10.1093\/nar\/gkm795","article-title":"STITCH: interaction networks of chemicals and proteins","volume":"36","author":"Kuhn","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2023020305200871100_btt321-B11","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/1471-2105-10-39","article-title":"Protein domain organisation: adding order","volume":"10","author":"Kummerfeld","year":"2009","journal-title":"BMC Bioinformatics"},{"key":"2023020305200871100_btt321-B12","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","article-title":"Clustal W and Clustal X version 2.0","volume":"23","author":"Larkin","year":"2007","journal-title":"Bioinformatics"},{"key":"2023020305200871100_btt321-B13","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/nbt0908-983","article-title":"Data completeness\u2014the Achilles heel of drug-target networks","volume":"26","author":"Mestres","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"2023020305200871100_btt321-B14","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1039\/b905821b","article-title":"The topology of drug-target interaction networks: implicit dependence on drug properties and target families","volume":"5","author":"Mestres","year":"2009","journal-title":"Mol. Biosyst."},{"key":"2023020305200871100_btt321-B15","doi-asserted-by":"crossref","first-page":"e30028","DOI":"10.1371\/journal.pone.0030028","article-title":"Modularity in protein complex and drug interactions reveals new polypharmacological properties","volume":"7","author":"Nacher","year":"2012","journal-title":"PLoS One"},{"key":"2023020305200871100_btt321-B16","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/S0969-2126(97)00260-8","article-title":"CATH\u2014a hierarchic classification of protein domain structures","volume":"5","author":"Orengo","year":"1997","journal-title":"Structure"},{"key":"2023020305200871100_btt321-B17","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1039\/C1MB05364G","article-title":"Promiscuous domains: facilitating stability of the yeast protein\u2013protein interaction network","volume":"8","author":"Pang","year":"2012","journal-title":"Mol. Biosyst."},{"key":"2023020305200871100_btt321-B18","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/S1359-6446(05)03666-4","article-title":"The druggable genome: an update","volume":"10","author":"Russ","year":"2005","journal-title":"Drug Discov. Today"},{"key":"2023020305200871100_btt321-B19","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1039\/c2mb05450g","article-title":"Predicting drug targets based on protein domains","volume":"8","author":"Wang","year":"2012","journal-title":"Mol. Biosyst."},{"key":"2023020305200871100_btt321-B20","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1006\/jmbi.2000.3786","article-title":"Estimating the number of protein folds and families from complete genome data","volume":"299","author":"Wolf","year":"2000","journal-title":"J. Mol. Biol."},{"key":"2023020305200871100_btt321-B21","doi-asserted-by":"crossref","first-page":"D730","DOI":"10.1093\/nar\/gkq1229","article-title":"DOMINE: a comprehensive collection of known and predicted domain-domain interactions","volume":"39","author":"Yellaboina","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"2023020305200871100_btt321-B22","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1038\/nbt1338","article-title":"Drug-target network","volume":"25","author":"Yildirim","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"2023020305200871100_btt321-B23","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1016\/j.febslet.2009.03.001","article-title":"A network medicine approach to human disease","volume":"583","author":"Zanzoni","year":"2009","journal-title":"FEBS Lett."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/29\/16\/1934\/49076635\/bioinformatics_29_16_1934.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/29\/16\/1934\/49076635\/bioinformatics_29_16_1934.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T05:22:14Z","timestamp":1675401734000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/29\/16\/1934\/199620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,5]]},"references-count":23,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2013,8,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btt321","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2013,8,15]]},"published":{"date-parts":[[2013,6,5]]}}}