Binding energy contributions of the conserved bridging water molecules in CDK2-inhibitor complexes: A combined QM/MM study

A combined quantum mechanics and molecular mechanics (QM/MM) method has been employed to investigate binding energy contributions of the conserved bridging water molecules in CDK2-inhibitor complexes. Calculations to eight selected CDK2-inhibitor complexes with each one containing the same bridging water molecule WAT145 show that the energy contribution of WAT145 varies with ligands, indicating that the energy contribution depends on the characteristic of the corresponding ligand. Calculations to the CDK2-inhibitor complex containing two bridging water molecules show that different bridging water molecules in the same complex offer different binding energy contributions, which is due to the difference of their local environment.