Modeling conformational flexibility of kinases in inactive states.

ABSTRACT: Kinase structures in the inactive "DFG-out" state provide a wealth of druggable binding site variants. The conformational plasticity of this state can be mainly described by different conformations of binding site-forming elements such as DFG motif, A-loop, P-loop, and αC-helix. Compared to DFG-in structures, DFG-out structures are largely underrepresented in the Protein Data Bank (PDB). Thus, structure-based drug design efforts for DFG-out inhibitors may benefit from an efficient approach to generate an ensemble of DFG-out structures. Accordingly, the presented modeling pipeline systematically generates homology models of kinases in several DFG-out conformations based on a sophisticated creation of template structures that represent the major states of the flexible structural elements. Ei

SUBMITTER: Schwarz D 

PROVIDER: S-EPMC6852311 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature