Document Type

Article

Publication Date

2-2009

Publication Title

Proteins

Volume

74

Issue

2

First Page

417

Last Page

424

Abstract

The use of predicted binding sites (binding sites calculated from the protein structure alone) is evaluated here as a tool to focus the docking of small molecule ligands into protein structures, simulating cases where the real binding sites are unknown. The resulting approach consists of a few independent docking runs carried out on small boxes, centered on the predicted binding sites, as opposed to one larger blind docking run that covers the complete protein structure. The focused and blind approaches were compared using a set of 77 known protein-ligand complexes and 19 ligand-free structures. The focused approach is shown to: (1) identify the correct binding site more frequently than blind docking; (2) produce more accurate docking poses for the ligand; (3) require less computational time. Additionally, the results show that very few real binding sites are missed in spite of focusing on only three predicted binding sites per target protein. Overall the results indicate that, by improving the sampling in regions that are likely to correspond to binding sites, the focused docking approach increases accuracy and efficiency of protein ligand docking for those cases where the ligand-binding site is unknown. This is especially relevant in applications such as reverse virtual screening and structure-based functional annotation of proteins.

Comments

This is the peer reviewed version of the following article: Ghersi D, Sanchez R, “Improving accuracy and efficiency of blind protein-ligand docking by focusing on predicted binding sites”, Proteins 2009, 74(2):417-24, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/prot.22154/abstract. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

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