DFGmodel: predicting protein kinase structures in inactive states for structure-based discovery of type-II inhibitors.

ABSTRACT: Protein kinases exist in equilibrium of active and inactive states, in which the aspartate-phenylalanine-glycine motif in the catalytic domain undergoes conformational changes that are required for function. Drugs targeting protein kinases typically bind the primary ATP-binding site of an active state (type-I inhibitors) or utilize an allosteric pocket adjacent to the ATP-binding site in the inactive state (type-II inhibitors). Limited crystallographic data of protein kinases in the inactive state hampers the application of rational drug discovery methods for developing type-II inhibitors. Here, we present a computational approach to generate structural models of protein kinases in the inactive conformation. We first perform a comprehensive analysis of all protein kinase structures deposit

SUBMITTER: Ung PM 

PROVIDER: S-EPMC4301084 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature