Homology modeling and docking study of cyclin-dependent kinase (CDK) 10

In order to understand the mechanisms of ligand binding and the interaction between the ligand and the cyclin-dependent kinase 10 (CDK10), a three-dimensional (3D) model of the CDK10 is generated based on the crystal structure of the cyclin-dependent kinase 2 (CDK2) (PDB code 1AQ1) by using InsightII/Homology module. With the aid of the molecular mechanics and molecular dynamics methods, the last refined model is obtained and is further assessed by PROFILE-3D and PROSTAT, which show that the refined model is reliable. With this model, a flexible docking study is performed and the results indicate that the Lys39 and Asp94 form hydrogen bonds and have strong nonbonding interaction with adenosine 5'-triphosphate (ATP). From the docking studies, we also suggest that the Leu141, Tyr21, and Val24 in CDK10 are three important determinant residues in binding as they have strong nonbonding interaction with ATP. The hydrogen bonding interactions also play an important role for the stability of the complex. Our results may be helpful for further experimental investigations.