One-class classification as a novel method of ligand-based virtual screening: the case of glycogen synthase kinase 3β inhibitors

Pavel V Karpov; Dmitry I Osolodkin; Igor I Baskin; Vladimir A Palyulin; Nikolay S Zefirov

doi:10.1016/j.bmcl.2011.09.051

One-class classification as a novel method of ligand-based virtual screening: the case of glycogen synthase kinase 3β inhibitors

Bioorg Med Chem Lett. 2011 Nov 15;21(22):6728-31. doi: 10.1016/j.bmcl.2011.09.051. Epub 2011 Sep 21.

Authors

Pavel V Karpov¹, Dmitry I Osolodkin, Igor I Baskin, Vladimir A Palyulin, Nikolay S Zefirov

Affiliation

¹ Department of Chemistry, Moscow State University, Leninskie Gory 1/3, Moscow 119991, Russia.

PMID: 21983440
DOI: 10.1016/j.bmcl.2011.09.051

Abstract

A virtual screening system based on one-class classification with molecular fingerprints as descriptors is developed and tested on a series of 1226 inhibitors and 209 noninhibitors of glycogen synthase kinase 3β (GSK-3β). The suggested system outperforms the ones based on pharmacophore hypothesis and molecular docking in a retrospective study. However, in a prospective study it should not be used as a sole classifier. The system is exceptionally useful for the identification of new scaffolds among the virtual screening results obtained with other methods.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Computer-Aided Design
Drug Design*
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Glycogen Synthase Kinase 3 / antagonists & inhibitors*
Glycogen Synthase Kinase 3 / metabolism
Glycogen Synthase Kinase 3 beta
Humans
Ligands
Models, Molecular
Neural Networks, Computer

Substances

Enzyme Inhibitors
Ligands
GSK3B protein, human
Glycogen Synthase Kinase 3 beta
Glycogen Synthase Kinase 3