Challenges of docking in large, flexible and promiscuous binding sites
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Cita com:
hdl:2117/90906
Tipus de documentArticle
Data publicació2016-10-15
EditorElsevier
Condicions d'accésAccés obert
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ProjecteESTUDIO DE FORMAS INUSUALES Y TENSIONADAS DE LOS ACIDOS NUCLEICOS DE INTERES BIOMEDICO Y BIOTECNOLOGICO. (MINECO-BIO2015-64802-R)
BioExcel - Centre of Excellence for Biomolecular Research (EC-H2020-675728)
BioExcel - Centre of Excellence for Biomolecular Research (EC-H2020-675728)
Abstract
After decades of work, the correct determination of the binding mode of a small molecule into a target protein is still a challenging problem, whose difficulty depends on: (i) the sizes of the binding site and the ligand; (ii) the flexibility of both interacting partners, and (iii) the differential solvation of bound and unbound partners. We have evaluated the performance of standard rigid(receptor)/flexible(ligand) docking approaches with respect to last-generation fully flexible docking methods to obtain reasonable poses in a very challenging case: soluble Epoxide Hydrolase (sEH), a flexible protein showing different binding sites. We found that full description of the flexibility of both protein and ligand and accurate description of solvation leads to significant improvement in the ability of docking to reproduce well known binding modes, and at the same time capture the intrinsic binding promiscuity of the protein.
CitacióKotev, Martin; Soliva, Robert; Orozco, Modesto. Challenges of docking in large, flexible and promiscuous binding sites. "Bioorganic & Medicinal Chemistry", 15 Octubre 2016, vol. 24, núm. 20, p. 4961-4969.
ISSN0968-0896
Versió de l'editorhttp://www.sciencedirect.com/science/article/pii/S0968089616306022
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