Discovery of Novel Noncovalent KRAS G12D Inhibitors through Structure-Based Virtual Screening and Molecular Dynamics Simulations.

ABSTRACT: The development of effective inhibitors targeting the Kirsten rat sarcoma viral proto-oncogene (KRAS^G12D) mutation, a prevalent oncogenic driver in cancer, represents a significant unmet need in precision medicine. In this study, an integrated computational approach combining structure-based virtual screening and molecular dynamics simulation was employed to identify novel noncovalent inhibitors targeting the KRAS^G12D variant. Through virtual screening of over 1.7 million diverse compounds, potential lead compounds with high binding affinity and specificity were identified using molecular docking and scoring techniques. Subsequently, 200 ns molecular dynamics simulations provided critical insights into the dynamic behavior, stability, and conformational changes of the

SUBMITTER: Du Z 

PROVIDER: S-EPMC10975070 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature