2026-04-17T05:53:38Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1219062025-11-19T10:41:54Zcom_2072_1057col_2072_478815col_2072_478908col_2072_478917

Detecting similar binding pockets to enable systems polypharmacology Duran Frigola, Miquel Siragusa, Lydia Ruppin, Eytan Barril Alonso, Xavier Cruciani, Gabriele Aloy, Patrick, 1972- Biologia computacional Disseny de medicaments Farmacologia Computational biology Drug design Pharmacology In the era of systems biology, multi-target pharmacological strategies hold promise for tackling disease-related networks. In this regard, drug promiscuity may be leveraged to interfere with multiple receptors: the so-called polypharmacology of drugs can be anticipated by analyzing the similarity of binding sites across the proteome. Here, we perform a pairwise comparison of 90,000 putative binding pockets detected in 3,700 proteins, and find that 23,000 pairs of proteins have at least one similar cavity that could, in principle, accommodate similar ligands. By inspecting these pairs, we demonstrate how the detection of similar binding sites expands the space of opportunities for the rational design of drug polypharmacology. Finally, we illustrate how to leverage these opportunities in protein-protein interaction networks related to several therapeutic classes and tumor types, and in a genome-scale metabolic model of leukemia. 2018-04-26T11:13:40Z 2018-04-26T11:13:40Z 2017-06-29 2018-04-26T11:13:40Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Reproducció del document publicat a: https://doi.org/10.1371/journal.pcbi.1005522 PLoS Computational Biology, 2017, vol. 13, num. 6, p. e1005522 https://doi.org/10.1371/journal.pcbi.1005522 info:eu-repo/grantAgreement/EC/FP7/614944/EU//SYSPHARMAD info:eu-repo/grantAgreement/EC/FP7/306240/EU//SYSTEMAGE cc-by (c) Duran Frigola, Miquel et al., 2017 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess Public Library of Science (PLoS) Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)