MOLECULAR DOCKING AND QSAR STUDIES ON CDK4 INHIBITORS USING IN SILICO TECHNIQUES

Abstract

Author(s): Anupama Pandrangi*

Cyclin-dependent kinases are a small family of serine/threonine protein kinases which control the cell cycle progression. Literature survey revealed that CDKs, their regulators, and substrates are the targets of genetic alteration in many human cancers. The best characterized case of such alteration is the p16-CDK4, 6/cyclin D-retinoblastoma pathway found in more than half of all human cancers. Therefore, CDK4 is an attractive target for the development of a novel anticancer agent. Computer aided drug design strategy has gained much prominence due to the fast and efficient means of studying protein-ligand interactions. A molecular docking was performed using Molegro Virtual Docker 6.0 with the CDK4 protein and the selected compounds from literature as ligands. QSAR toxicity analysis has been performed using FAF Drugs ADME/tox filtering server. Considering the molecular properties of the ligands, higher inhibitory activity is associated with reduced molecular flexibility, as measured by lower polar surface area (TPSA), LogP, lower hydrogen bond counts, confirming the capability of the compounds for binding at the active site of the receptor.