Understanding the influence of AMG 510 on the structure of KRAS^G12C empowered by molecular dynamics simulation.

ABSTRACT: The KRAS^G12C mutant is often associated with human cancers, and AMG 510 as a promising covalent inhibitor of KRAS^G12C has achieved surprising efficacy in clinical trials. However, the interaction mechanism between KRAS^G12C and AMG 510 is not completely understood. Here, we performed all-atom molecular dynamics simulations on the complex of KRAS^G12C-AMG 510 to explore the influence of this covalent inhibitor on the conformational change of KRAS^G12C. A PCA (Principal Component Analysis) model was constructed based on known KRAS crystal structures to distinguish different conformations (active, inactive, and other). By mapping simulation trajectories onto the PCA model, we observed that the conformations of KRAS^G12C bound with

SUBMITTER: Li Y 

PROVIDER: S-EPMC8894142 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature