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.

中文翻译：

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使用 SIRT1 对白藜芦醇衍生物进行分子建模以刺激脱乙酰酶活性

背景：白藜芦醇是一种存在于植物中的多酚，已被认为通过激活 SIRT1 具有潜在的治疗作用，SIRT1 是哺乳动物 NAD+ 依赖性脱乙酰酶的重要成员。然而，尚未研究白藜芦醇衍生物如何增强其对特定底物的活性。本研究旨在评估白藜芦醇及其衍生物与SIRT1作为靶蛋白的相互作用类型，以及找出与SIRT1最奇怪的相互作用的最佳配体。材料和方法：在本研究中，我们使用 AutoDock Vina 进行广泛的分子对接分析，比较评估作为配体的白藜芦醇衍生物（ZINC 数据库中的 22 个分子）与作为受体的 SIRT1（PDB ID：5BTR）的相互作用。ChemDraw 和 Chem3D 工具用于准备所有配体的 3D 结构，并通过 MM2 力场大力最小化它们。结果：分子对接和可视化表明，白藜芦醇衍生物的构象变化显着影响对接结果的参数。通过对白藜芦醇衍生物和 SIRT1 受体的对接分析，发现了几种类型的相互作用，包括常规氢键、碳-氢键、Pi-供体氢键和 Pi-烷基。具有 ZINC ID：ZINC230079516 的白藜芦醇 4'-(6-没食子酰基葡萄糖苷) 与 SIRT1 催化结构域 (CD) 的结合能分数较高 (-46.8608 kJ/mol) 的可能激活效果在 SIRT1 的最大值下实现，如下所示与白藜芦醇及其其他衍生物相比。结论：最后，白藜芦醇4'-(6-没食子酰基葡萄糖苷)作为白藜芦醇的衍生物，与SIRT1的CD稳定相互作用，可能是SIRT1的潜在有效激活剂。