MM-PBSA calculations offer quantitative insights into protein-ligand binding energetics, complementing docking, and MD simulation results. Table presents binding free energy values, with the vitamin D3-SIRT1 complex exhibiting a higher binding free energy compared to the vitamin D2-SIRT1 complex. The MD results, show vitamin D3's stability and burial in the SIRT1 pocket, align with the high contribution of electrostatic interactions to complex stabilization. Non-polar interactions also stabilize the vitamin D3-SIRT1 complex when compared to the vitamin D2-SIRT1 complex. However, the higher polar interaction in vitamin D3-SIRT1 leads to a decrease in other forms of interaction. Importantly, MM-PBSA binding free energy values suggest that vitamin D3 is more stable than vitamin D2 as shown by their binding energies.