Журнал прикладной биоинформатики и вычислительной биологии

Structural Analysis of Noncovalent Interactions in CDK2 Inhibitor Complexes

Vijina Chakkyarath*

A huge number of ATP site directed, small molecular inhibitors have been synthesized and tested for finding their biological activity against different types of kinases more than the past three decades. Cyclin dependent kinases are also one of the significant targets for drug discovery. Three dimensional structures of 6 CDK2 ATP complexes and 50 CDK2 inhibitor complexes have taken from PDB and IC50 values available for 23 of these complexes. As binding to ATP site and the biological activity may be dependent on the different noncovalent interactions such as hydrogen bonds, hydrophobic bonds and electrostatic, Vaanderwaals such as other interactions. In the present work we have analyzed these interactions in the CDK2-ATP complexes as well as CDK2 inhibitor complexes. Based on these interactions we have developed multiple regression models to account for the experimentally observed IC50 values. We have made extensive analysis of the amino acids ATP contacts amino acids inhibitor contacts. Also the extend of similarity between the various ligands has been quantified using 2D and 3D analysis methods.