期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 24, 期 20, 页码 4961-4969出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2016.08.010
关键词
Induced-fit docking; PELE simulations; Soluble Epoxide Hydrolase; Benchmark
资金
- Fundacio Marato TV3
- BioExcel project and Human Brain Flagship project
- Spanish MINECO [BIO2015/64802-R]
- Severo Ochoa Award of Excellence from MINECO (Government of Spain)
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. (C) 2016 Elsevier Ltd. All rights reserved.
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