Fast docking using the CHARMM force field with EADock DSS.

Details

Serval ID
serval:BIB_50CA4A88BB50
Type
Article: article from journal or magazin.
Collection
Publications
Title
Fast docking using the CHARMM force field with EADock DSS.
Journal
Journal of Computational Chemistry
Author(s)
Grosdidier A., Zoete V., Michielin O.
ISSN
1096-987X (Electronic)
ISSN-L
0192-8651
Publication state
Published
Issued date
2011
Volume
32
Number
10
Pages
2149-2159
Language
english
Notes
Publication types: JOURNAL ARTICLE
Abstract
The prediction of binding modes (BMs) occurring between a small molecule and a target protein of biological interest has become of great importance for drug development. The overwhelming diversity of needs leaves room for docking approaches addressing specific problems. Nowadays, the universe of docking software ranges from fast and user friendly programs to algorithmically flexible and accurate approaches. EADock2 is an example of the latter. Its multiobjective scoring function was designed around the CHARMM22 force field and the FACTS solvation model. However, the major drawback of such a software design lies in its computational cost. EADock dihedral space sampling (DSS) is built on the most efficient features of EADock2, namely its hybrid sampling engine and multiobjective scoring function. Its performance is equivalent to that of EADock2 for drug-like ligands, while the CPU time required has been reduced by several orders of magnitude. This huge improvement was achieved through a combination of several innovative features including an automatic bias of the sampling toward putative binding sites, and a very efficient tree-based DSS algorithm. When the top-scoring prediction is considered, 57% of BMs of a test set of 251 complexes were reproduced within 2 Å RMSD to the crystal structure. Up to 70% were reproduced when considering the five top scoring predictions. The success rate is lower in cross-docking assays but remains comparable with that of the latest version of AutoDock that accounts for the protein flexibility. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011.
Pubmed
Web of science
Create date
25/10/2011 9:35
Last modification date
03/03/2018 17:09
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