Binding Mechanism of Inhibitors to CDK6 Deciphered by Multiple Independent Molecular Dynamics Simulations and Free Energy Predictions.

ABSTRACT: Cyclin-dependent kinase 6 (CDK6) has been identified as a potential drug target in various types of cancers. In our current study, multiple independent molecular dynamics simulations of four separate replicates and computations of binding free energies are carried out to decipher the binding mechanisms of three inhibitors, LQQ, 6ZV, and 0RS, to CDK6. The dynamic analyses indicate that the presence of inhibitors influences conformational alterations, motion modes, and the internal dynamics of CDK6. Binding free energies computed using the molecular mechanics generalized Born surface area (MM-GBSA) approach with four GB models demonstrate that hydrophobic interactions play essential roles in inhibitor-CDK6 binding. The computations of residue-based free energy decomposition verify that the s

SUBMITTER: Wang L 

PROVIDER: S-EPMC11901890 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature