Challenges of docking in large, flexible and promiscuous binding sites
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...
| Autores: | , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Universitat Politècnica de Catalunya (UPC) |
| Repositorio: | UPCommons. Portal del coneixement obert de la UPC |
| Idioma: | inglés |
| OAI Identifier: | oai:upcommons.upc.edu:2117/90906 |
| Acceso en línea: | https://hdl.handle.net/2117/90906 https://dx.doi.org/10.1016/j.bmc.2016.08.010 |
| Access Level: | acceso abierto |
| Palabra clave: | Protein binding Simulations Induced-fit docking PELE simulations Soluble Epoxide Hydrolase Benchmark Proteïnes--Investigació Simulació, Mètodes de Àrees temàtiques de la UPC::Enginyeria biomèdica |
| Sumario: | 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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