When assessing the docking results of vitamin D2 and D3 with grid settings, only SIRT1 intermolecular interactions . Hydrating the proteins led to an increase in binding affinity, particularly evident in SIRT1 (4ZZI), where vitamin D2 exhibited the strongest affinity of -48.33 kJ/mol compared to vitamin D3 with a binding affinity of -45.94 kJ/mol. These findings suggest that water molecules could significantly influence the design of anti-aging molecules, with the interaction of SIRT1 with vitamin D2 favored by water molecules in the active site.