Structural Bioinformatics Approach of Cyclin-Dependent Kinases 1 and 3 Complexed with Inhibitors.

Abstract

The cyclin-dependent kinases or CDKs participate in the regulation of both the cell progression cycle and the RNA polymerase-II transcription cycle. In several human tumours deregulation of CDK-related mechanisms have been detected, e.g., overexpression of cyclins or deletion of genes encoding for CKIs. Regarding these observations, CDKs came up to be interesting targets for elaboration of novel antitumour drugs. Based on the importance of the CDKs, this research aimed to describe, to characterize and to compare the molecular models of CDK1 and CDK3. Since the structures of human CDK1 and CDK3 are unavailable in the Protein Data Bank -PDB, homology models were created based on the CDK2 as the template, once they share a substantial identity. The structural studies of the CDK1 and CDK3 biding sites were conducted by molecular docking with 15 different CDK inhibitors previously identified to CDK2. This study allowed the understanding of the structure of the complexes between CDK1/ CDK3 with inhibitors. The knowledge of their structural features mainly the biding sites might be useful to discovery and rationalization of drug design process.