Resveratrol and its derivatives have been shown to display beneficial effects to neurodegenerative diseases. However, the molecular mechanism of resveratrol and its derivatives on prion conformational conversion is poorly understood. In this work, the interaction mechanism between prion and resveratrol as well as its derivatives was investigated using steady-state fluorescence quenching, Thioflavin T binding assay, Western blotting, and molecular dynamics simulation. Protein fluorescence quenching method and Thioflavin T assay revealed that resveratrol and its derivatives could interact with prion and interrupt prion fibril formation. Molecular dynamics simulation results indicated that resveratrol can stabilize the PrP_127–147 peptide mainly through π–π stacking interactions between resveratrol and Tyr128. The hydrogen bonds interactions between resveratrol and the PrP_127–147 peptide could further reduce the flexibility and the propensity to aggregate. The results of this study not only can provide useful information about the interaction mechanism between resveratrol and prion, but also can provide useful clues for further design of new inhibitors inhibiting prion aggregation.

中文翻译：

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白藜芦醇及其衍生物对Pri性纤颤抑制机制的实验和理论研究

白藜芦醇及其衍生物已显示出对神经退行性疾病的有益作用。然而，人们对白藜芦醇及其衍生物对病毒构象转化的分子机理了解甚少。在这项工作中，使用稳态荧光猝灭，硫黄素T结合测定，蛋白质印迹和分子动力学模拟研究了ion病毒与白藜芦醇及其衍生物之间的相互作用机理。蛋白荧光猝灭法和硫黄素T法检测结果表明白藜芦醇及其衍生物可与病毒相互作用，阻断病毒原纤维的形成。分子动力学模拟结果表明，白藜芦醇可以稳定PrP _127–147肽主要是通过白藜芦醇和Tyr128之间的π–π堆积相互作用来实现的。白藜芦醇和PrP _127-147肽之间的氢键相互作用可能会进一步降低柔韧性和聚集倾向。这项研究的结果不仅可以提供有关白藜芦醇与病毒之间相互作用机理的有用信息，而且可以为进一步设计抑制pr病毒聚集的新抑制剂提供有用的线索。