Automated docking of highly flexible ligands by genetic algorithms: A critical assessment

TitleAutomated docking of highly flexible ligands by genetic algorithms: A critical assessment
Publication TypeJournal Article
Year of Publication2004
AuthorsCecchini M., Kolb P., Majeux N., Caflisch A.
JournalJournal of Computational Chemistry
Volume25
Issue3
Pagination412-422
Date Published2004 Feb
Type of ArticleResearch Article
ISSN0192-8651
KeywordsAlgorithms, Binding Sites, Crystallography, X-Ray, Estrogen Receptor beta, HIV Protease Inhibitors, Humans, Ligands, Models, Molecular, Protein Binding, Protein Conformation, Receptors, Estrogen, Thrombin
Abstract

An improved version of the fragment-based flexible ligand docking approach SEED-FFLD is tested on inhibitors of human immunodeficiency virus type 1 protease, human α-thrombin and the estrogen receptor β. The docking results indicate that it is possible to correctly reproduce the binding mode of inhibitors with more than ten rotatable bonds if the strain in their covalent geometry upon binding is not large. A high degree of convergence towards a unique binding mode in multiple runs of the genetic algorithm is proposed as a necessary condition for successful docking.

DOI10.1002/jcc.10384
pubindex

0054

Alternate JournalJ Comput Chem
PubMed ID14696075
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