Background:Resveratrol is a polyphenol that is found in plants and has been proposed
to have a potential therapeutic effect through the activation of SIRT1, which is a crucial
member of the mammalian NAD+ -dependent deacetylases. However, how its activity is enhanced
toward specific substrates by resveratrol derivatives has not been studied. This study
aimed to evaluate the types of interaction of resveratrol and its derivatives with SIRT1 as the
target protein, as well as to find out the best ligand with the strangest interaction with SIRT1.Materials and Methods:In this study, we employed the extensive molecular docking analysis
using AutoDock Vina to comparatively evaluate the interactions of resveratrol derivatives (22
molecules from the ZINC database) as ligands with SIRT1 (PDB ID: 5BTR) as a receptor. The
ChemDraw and Chem3D tools were used to prepare 3D structures of all ligands and energetically
minimize them by the MM2 force field.Results:The molecular docking and visualizations showed that conformational change in
resveratrol derivatives significantly influenced the parameter for docking results. Several types
of interactions, including conventional hydrogen bonds, carbon-hydrogen bonds, Pi-donor hydrogen
bonds, and Pi-Alkyl, were found via docking analysis of resveratrol derivatives and
SIRT1 receptors. The possible activation effect of resveratrol 4'-(6-galloylglucoside) with ZINC
ID: ZINC230079516 with higher binding energy score (-46.8608 kJ/mol) to the catalytic domain
(CD) of SIRT1 was achieved at the maximum value for SIRT1, as compared to resveratrol
and its other derivatives.Conclusion:Finally, resveratrol 4'-(6-galloylglucoside), as a derivative for resveratrol, has stably
interacted with the CD of SIRT1 and might be a potential effective activator for SIRT1.