Description and assessment of a model for GSK-3beta database virtual screening.
Molecular docking was used in order to prioritize organic syntheses or experimental evaluations. Different GSK-3beta protein models were generated in silico from a known X-ray structure. A set of 42 known inhibitors were then flexibly docked into each rigid model and re-scored with various functions, which led to different rankings. The biological activities of the chemicals were then compared to each set of results and one of the rigid models emerged in combination with two scoring functions as giving the best correlation. This methodology constitutes an easy and accurate way to generate reliable models for virtual database screening.
Ventimila
Nadege
N
UMR 5248 CBMN Chimie et Biologie des Membranes et Nanoobjets, CNRS-Université Bordeaux 1-ENITAB, IECB, Pessac, France.
Dupont
Pierre-Yves
PY
Laguerre
Michel
M
Dessolin
Jean
J
D000465:Algorithms; D000818:Animals; D019295:Computational Biology; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008956:Models, Chemical; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D021281:Quantitative Structure-Activity Relationship; D014584:User-Computer Interface
D047428:Protein Kinase Inhibitors; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3