2026-04-13T07:16:44Zhttps://recercat.cat/oai/requestoai:recercat.cat:2445/1219062025-11-19T10:41:54Zcom_2072_1057col_2072_478815col_2072_478908col_2072_478917
RECERCAT
author
Duran Frigola, Miquel
author
Siragusa, Lydia
author
Ruppin, Eytan
author
Barril Alonso, Xavier
author
Cruciani, Gabriele
author
Aloy, Patrick, 1972-
2018-04-26T11:13:40Z2018-04-26T11:13:40Z2017-06-292018-04-26T11:13:40Z
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.
cc-by (c) Duran Frigola, Miquel et al., 2017 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess
Biologia computacional
Disseny de medicaments
Farmacologia
Computational biology
Drug design
Pharmacology
Detecting similar binding pockets to enable systems polypharmacology
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion