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cc-by-nc-nd (c) Elsevier, 2016
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/110714

Challenges of docking in large, flexible and promiscuous binding sites

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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.

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KOTEV, Martin, SOLIVA, Robert, OROZCO LÓPEZ, Modesto. Challenges of docking in large, flexible and promiscuous binding sites. _Bioorganic & Medicinal Chemistry_. 2016. Vol. 24, núm. 20, pàgs. 4961-4969. [consulta: 20 de gener de 2026]. ISSN: 0968-0896. [Disponible a: https://hdl.handle.net/2445/110714]

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