Discovery of novel checkpoint kinase 1 inhibitors by virtual screening based on multiple crystal structures.

ABSTRACT: Incorporating receptor flexibility is considered crucial for improvement of docking-based virtual screening. With an abundance of crystallographic structures freely available, docking with multiple crystal structures is believed to be a practical approach to cope with protein flexibility. Here we describe a successful application of the docking of multiple structures to discover novel and potent Chk1 inhibitors. Forty-six Chk1 structures were first compared in single structure docking by predicting the binding mode and recovering known ligands. Combinations of different protein structures were then compared by recovery of known ligands and an optimal ensemble of Chk1 structures were selected. The chosen structures were used in the virtual screening of over 60 000 diverse compounds for Chk1

SUBMITTER: Li Y 

PROVIDER: S-EPMC3244973 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature