Abstract
Cyclin-dependent kinases (CDKs) are crucial for controlling the cell cycle, and many malignancies are linked to CDK dysfunction. Therefore, CDKs are desirable targets for cancer treatment. Since abnormal expression of CDK4/6 is the etiology of glioblastoma, it is imperative to investigate the mechanism underlying CDK4/6 selectivity for inhibitors compared to CDK1/2, another member of the family. This study used a range of molecular docking and bioinformatics techniques to characterize the specific efficacy of ligands as inhibitors and their interaction with CDK6. Ligand-based virtual screening was performed using 6OQL'ligand. Using Maestro 12.5, ligands were docked to the interaction site of CDK6 with a reference co-crystallized ligand (CCL). The ligands were analyzed for absorption, distribution, metabolism, excretion, and toxicity (ADMET). Using density functional theory (DFT) analysis, the selected ligands were found to have substantial stability. One ligand, Mol_370, which closely resembles the characteristics of CCL, was simulated using molecular dynamics. The results revealed that amino acids and ligands interact at the CDK6 inhibitor-binding site via typical chemical interactions, such as hydrophobic interactions and hydrogen bonds, as demonstrated by the docking data. MD simulations revealed that Mol_ 370 is compatible with CCL, leading to changes in both structure and function. In conclusion, this study offers significant insights into the development and refinement of inhibitors that can successfully target CDK6 and produce novel cancer treatments.