A Definitive Pharmacophore Modelling Study on CDK2 ATP Pocket Binders: Tracing the Path of New Virtual High-Throughput Screenings

Cyclin Dependent Kinases-2 (CDK2) are members of serine/threonine protein kinases family. They play an important role in the regulation events of the eukaryotic cell division cycle, especially during the G1 to S phase transition. Experimental evidence indicate that excessive expression of CDK2s should cause abnormal cell cycle regulation. Therefore, since a long time, CDK2s have been considered potential therapeutic targets for cancer therapy. In this work, onehundred and forty-nine complexes of inhibitors bound in the CDK2-ATP pocket were submitted to short MD simulations (10ns) and free energy calculation. Comparison with experimental data (K<sub>i</sub>, K<sub>d</su…