In Silico Evaluation of Vitamin D3 as a Dual Inhibitor of CDK2 and Bcl-2 in Colorectal Cancer
Abstract
Background: The potential anticancer properties of vitamin D3 (cholecalciferol) have garnered growing interest. Epidemiological and preclinical studies suggest an inverse correlation between vitamin D3 levels and CRC incidence. However, the precise molecular mechanisms and direct targets through which vitamin D3 exerts anticancer effects remain inadequately characterized. Aim: This study aimed to investigate the dual-targeting potential of vitamin D3 against two key oncogenic proteins involved in the pathogenesis of CRC: cyclin-dependent kinase 2 (CDK2), a critical regulator of cell cycle progression, and B-cell lymphoma 2 (Bcl-2), an anti-apoptotic protein implicated in tumor survival. Method: Molecular docking was performed to assess the binding affinity of vitamin D3 to CDK2 and Bcl-2. Molecular dynamics simulations were used to evaluate the stability of the docked complexes over time. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis was performed to predict the pharmacokinetics and safety profile of vitamin D3. Results: Docking analysis revealed strong binding affinities of vitamin D3 to both CDK2 (-9.5 kcal/mol) and Bcl-2 (-8.2 kcal/mol), suggesting stable interactions at the ATP-binding site of CDK2 and the BH3-binding groove of Bcl-2. Molecular dynamics simulations confirmed the conformational stability and sustained interactions of vitamin D3 with both targets throughout the simulation period. ADMET predictions indicated favorable oral…
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