Interaction mode and selectivity of the 2PU inhibitor with the CDK4 and CDK2 cyclin-dependant kinases: A molecular dynamics study

This paper is focused on a computational study of an inhibitor which shows good selectivity for CDK4 relative to CDK2. Using molecular dynamics and free-energy calculations, the main protein residues interacting with the ligand are identified, the conformational and dynamical changes are established, the role of H bonds is examined and the binding free energies are obtained for both complexes. Differences in binding mode are discussed and related to selectivity.