Selectivity analysis of CDK2 inhibitors via molecular dynamics of CDK1 and CDK2
Dmitrii O Shkil1, Anastasia S Fokina2, Dariy T Asainov1
1Moscow Institute of Physics and Technology, Institutskiy per. 9, Dolgoprudny, 141701, Russia.
Abstract:
Cyclin-dependent kinases (CDKs) are pivotal regulators of the cell cycle and attractive therapeutic targets, particularly in breast cancer treatment. However, achieving selectivity among closely related CDKs, such as CDK2/CDK1, remains a significant challenge in drug discovery. In this study, we leverage molecular dynamics simulations and protein-ligand interaction analyses to uncover the structural and pharmacophoric determinants that drive selective inhibition of these kinases. By comparing known inhibitors and their contacts with CDK1 and CDK2, we identify critical pharmacophoric features essential for achieving target-specific selectivity. These findings provide valuable hypotheses into the design of next-generation CDK inhibitors with improved therapeutic profiles, addressing the pressing need for selective and effective cancer therapies.
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