Attracting cavities for docking. Replacing the rough energy landscape of the protein by a smooth attracting landscape.

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Version: Final published version
Serval ID
serval:BIB_2D11A0764FB8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Attracting cavities for docking. Replacing the rough energy landscape of the protein by a smooth attracting landscape.
Journal
Journal of Computational Chemistry
Author(s)
Zoete V., Schuepbach T., Bovigny C., Chaskar P., Daina A., Röhrig U.F., Michielin O.
ISSN
1096-987X (Electronic)
ISSN-L
0192-8651
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
37
Number
4
Pages
437-447
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Molecular docking is a computational approach for predicting the most probable position of ligands in the binding sites of macromolecules and constitutes the cornerstone of structure-based computer-aided drug design. Here, we present a new algorithm called Attracting Cavities that allows molecular docking to be performed by simple energy minimizations only. The approach consists in transiently replacing the rough potential energy hypersurface of the protein by a smooth attracting potential driving the ligands into protein cavities. The actual protein energy landscape is reintroduced in a second step to refine the ligand position. The scoring function of Attracting Cavities is based on the CHARMM force field and the FACTS solvation model. The approach was tested on the 85 experimental ligand-protein structures included in the Astex diverse set and achieved a success rate of 80% in reproducing the experimental binding mode starting from a completely randomized ligand conformer. The algorithm thus compares favorably with current state-of-the-art docking programs.
Keywords
Algorithms, Ligands, Molecular Docking Simulation, Proteins/chemistry, Thermodynamics
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2016 15:32
Last modification date
20/08/2019 13:12
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