The Molecular Docking and Molecular Dynamic Effects of Omeprazole on CDKs 2, 4, and 6 as a Potential CDK Inhibitor in Cancer Treatment

Abstract

Introduction: Cyclin-dependent kinases (CDKs) are serine/threonine kinase proteins that regulate the cell cycle through phosphorylation and dephosphorylation. These proteins are a main target in cancer therapy. This study investigated the effect of omeprazole on CDK2, CDK4, and CDK6 through simulation studies. Methods: To investigate the interaction between omeprazole and CDK2, 4, and 6, the threedimensional structure of omeprazole was obtained from PubChem, and the structures of CDK2, 4, and 6 were acquired from RCSB servers. The proteins were then simulated for 50 nanoseconds using the GROMACS 2021 platform before the docking process. Next, Autodock v.4.2.6 software was used to bind omeprazole as a ligand to these proteins, and a molecular dynamics simulation of the resulting protein-ligand complex was conducted using GROMACS after the docking process. Results: Omeprazole exhibited a high affinity for interacting with CDK2, 4, and 6, mainly occurring in the ATP binding site of CDK4. However, the docking of omeprazole in the CDKs induced conformational changes in their structures, which could potentially affect their function and lead to cell cycle arrest. Conclusion: Omeprazole, which is a proton pump inhibitor, can induce cell cycle arrest by interacting with the ATP-binding site of CDK4. Moreover, it can also induce conformational changes in CDK2, CDK4, and CDK6 through high-affinity interactions with specific amino acid residues.