{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T15:24:05Z","timestamp":1764689045544},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"24","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":411,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: The inherent promiscuity of small molecules towards protein targets impedes our understanding of healthy versus diseased metabolism. This promiscuity also poses a challenge for the pharmaceutical industry as identifying all protein targets is important to assess (side) effects and repositioning opportunities for a drug.<\/jats:p>\n               <jats:p>Results: Here, we present a novel integrated structure- and system-based approach of drug-target prediction (iDTP) to enable the large-scale discovery of new targets for small molecules, such as pharmaceutical drugs, co-factors and metabolites (collectively called \u2018drugs\u2019). For a given drug, our method uses sequence order\u2013independent structure alignment, hierarchical clustering and probabilistic sequence similarity to construct a probabilistic pocket ensemble (PPE) that captures promiscuous structural features of different binding sites on known targets. A drug\u2019s PPE is combined with an approximation of its delivery profile to reduce false positives. In our cross-validation study, we use iDTP to predict the known targets of 11 drugs, with 63% sensitivity and 81% specificity. We then predicted novel targets for these drugs\u2014two that are of high pharmacological interest, the peroxisome proliferator-activated receptor gamma and the oncogene B-cell lymphoma 2, were successfully validated through in\u00a0vitro binding experiments. Our method is broadly applicable for the prediction of protein-small molecule interactions with several novel applications to biological research and drug development.<\/jats:p>\n               <jats:p>Availability and implementation: The program, datasets and results are freely available to academic users at http:\/\/sfb.kaust.edu.sa\/Pages\/Software.aspx.<\/jats:p>\n               <jats:p>Contact: \u00a0xin.gao@kaust.edu.sa and stefan.arold@kaust.edu.sa<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btv477","type":"journal-article","created":{"date-parts":[[2015,8,19]],"date-time":"2015-08-19T02:39:25Z","timestamp":1439951965000},"page":"3922-3929","source":"Crossref","is-referenced-by-count":15,"title":["An integrated structure- and system-based framework to identify new targets of metabolites and known drugs"],"prefix":"10.1093","volume":"31","author":[{"given":"Hammad","family":"Naveed","sequence":"first","affiliation":[{"name":"1 Computer, Electrical and Mathematical Sciences and Engineering Division,"},{"name":"2 Computational Bioscience Research Center,"}]},{"given":"Umar S.","family":"Hameed","sequence":"additional","affiliation":[{"name":"3 Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia,"}]},{"given":"Deborah","family":"Harrus","sequence":"additional","affiliation":[{"name":"4 Inserm U1054, Centre de Biochimie Structurale and"},{"name":"5 CNRS UMR5048, Universit\u00e9s Montpellier 1 & 2, Montpellier, France"}]},{"given":"William","family":"Bourguet","sequence":"additional","affiliation":[{"name":"4 Inserm U1054, Centre de Biochimie Structurale and"},{"name":"5 CNRS UMR5048, Universit\u00e9s Montpellier 1 & 2, Montpellier, France"}]},{"given":"Stefan T.","family":"Arold","sequence":"additional","affiliation":[{"name":"2 Computational Bioscience Research Center,"},{"name":"3 Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia,"}]},{"given":"Xin","family":"Gao","sequence":"additional","affiliation":[{"name":"1 Computer, Electrical and Mathematical Sciences and Engineering Division,"},{"name":"2 Computational Bioscience Research Center,"}]}],"member":"286","published-online":{"date-parts":[[2015,8,18]]},"reference":[{"key":"2023051307183360600_btv477-B1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1042\/BJ20140298","article-title":"How to find a leucine in a haystack? 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