Current Computer-Aided Drug DesignCurrent Computer-Aided Drug DesignCurrent Computer-Aided Drug Design1573-40991875-6697Bentham Science64443310.2174/0115734099258321231003161602ChemistryResearch ArticleMolecular Modelling of Resveratrol Derivatives with SIRT1 for the Stimulation of Deacetylase ActivityZamaniMozhdehinfo@benthamscience.netMokarramPoonehinfo@benthamscience.netJamshidiMehdiinfo@benthamscience.netSiriMorvaridinfo@benthamscience.netGhasemiHadiinfo@benthamscience.netAutophagy Research Center, Department of Biochemistry, School of Medicine, Shiraz University of Medical SciencesAutophagy Research Center, Department of Biochemistry, School of Medicine,, Shiraz University of Medical SciencesInstitute für Chemie, Universität OldenburgAutophagy Research Center, Department of Biochemistry, School of Medicine,, Shiraz University of Medical Sciences,0106202420694395407012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://rjeid.com/1573-4099/article/view/644433

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.

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