Identification of functional substates of KRas during GTP hydrolysis with enhanced sampling simulations
Juan Zeng, Jian Chen, Fei Xia, Qiang Cui, Xianming Deng, Xin Xu
Abstract
has more than two stable substates in solution, pointing to a conformation-selection mechanism for complexation with GEFs. Based on these results, some specific inhibition strategies for targeting the binding sites of the high-energy substates of KRas during GTP hydrolysis are discussed.
Topics & Concepts
KRASGTP'HRASChemistryHydrolysisMolecular dynamicsConformational isomerismStereochemistryComputational chemistryBiochemistryMoleculeEnzymeMutationGeneOrganic chemistryProtein Kinase Regulation and GTPase SignalingEnzyme Structure and FunctionMelanoma and MAPK Pathways