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Authors:
M. Cecchini; P. Kolb; N. Majeux; A. Caflisch

Journal: J Comput Chem
Year: 2004
Volume: 25
Issue: 3
Pages: 412-422
DOI: 10.1002/jcc.10384
Type of Publication: Journal Article

Keywords:
Algorithms; 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.