漆黄素抗骨关节炎作用机制的分子对接研究  

Molecular docking study on the anti-osteoarthritis mechanism of Fisetin

作　　者：郭小华[1] 叶民珠[1] 吴龙火[1] GUO Xiao-hua;YE Min-zhu;WU Long-huo(Pharmacy College,Gannan Medical University,Ganzhou,Jiangxi 341000)

机构地区：[1]赣南医学院药学院,江西赣州341000

出　　处：《赣南医学院学报》2021年第8期832-837,共6页JOURNAL OF GANNAN MEDICAL UNIVERSITY

基　　金：国家自然科学基金资助项目(82060407);江西省教育厅科学技术研究项目(GJJ201524);江西省卫生计生委中医药科研项目(2017A246)。

摘　　要：目的:用分子对接软件对漆黄素与10个抗骨关节炎靶蛋白进行分子模拟对接研究,探讨其可能的抗骨关节炎作用机制,并根据配体与受体相互作用为漆黄素的结构修饰提供一定指导。方法:采用AutoDock 4.2分子对接软件,模拟漆黄素与10个抗骨关节炎靶蛋白的相互作用和结合模式,并将靶蛋白中的原始配体与对应的靶蛋白进行重对接实验。以估计抑制常数(Ki值)或结合自由能(△G_(bind))等对接数据为参考,同时比较分子对接构象,分析漆黄素与各靶蛋白的结合模式。结果:漆黄素与TNF-α受体分子对接Ki值为7.10×10^(-2)μmol·L^(-1),远小于相应原始配体分子对接Ki值(5.27×10^(-1)μmol·L^(-1))。漆黄素与iNOS受体分子对接Ki值为2.54μmol·L^(-1),是其相应原始配体分子对接Ki值(7.16×10^(-2)μmol·L^(-1))的35倍。漆黄素与TNF-α受体分子对接时,空间上与TNF-α受体的活性位点相互匹配,分子对接构象稳定,漆黄素结构中的3个酚羟基均与受体活性位点中的关键氨基酸形成了氢键相互作用力。漆黄素与iNOS受体分子对接时,占据了iNOS受体的细长活性腔,对圆形活性口袋作用较弱。结论:漆黄素对抗骨关节炎靶点的作用有一定的选择性,漆黄素与TNF-α受体结合作用强,表现出很强的虚拟抑制活性,可能是漆黄素发挥抗骨关节炎作用的主要作用靶点。漆黄素的3位羟基是提高其抗骨关节炎活性的主要结构修饰位点。Objective:The molecular docking study of Fisetin with 10 antiosteoarthritis target proteins was carried out by molecular docking software,the possible mechanism of the antiosteoarthritis action of Fisetin was discussed,and the guidance for the structural modification of Fisetin was provided according to the interaction between ligand and receptor.Methods:AutoDock 4.2 molecular docking software was used to simulate the interaction and binding mode of Fisetin with 10 antiosteoarthritis target proteins,and the redocking experiment was conducted between the original ligand in the target protein and the corresponding target protein.The docking datas such as Ki value or △G_(bind) value were used as reference,and the molecular docking conformations were compared to analyze the binding patterns of Fisetin and target proteins.Results:The molecular docking Ki value of Fisetin and TNF-α receptor was 7.10×10^(-2)μmol·L^(-1),which was much lower than that of the corresponding original ligand(5.27×10^(-1)μmol·L^(-1)).The molecular docking Ki value of Fisetin and iNOS receptor was 2.54μmol·L^(-1),which was 35 times that of the corresponding original ligand(7.16×10^(-2)μmol·L^(-1)).When Fisetin was docked with TNF-αreceptor,it was spatially matched with the active site of TNF-αreceptor,and the conformation of molecular docking was stable.The three phenolic hydroxyl groups in the structure of Fisetin formed hydrogen bond interaction with the key amino acids in the active site of the receptor.When Fisetin was docked with iNOS receptor,it occupied the slender active cavity of iNOS receptor,and had a weak effect on the round active pocket.Con⁃clusion:The results of molecular docking showed that Fisetin had a selective effect on the targets of antiosteoarthritis.Fisetin had a strong binding effect on TNF-α receptor and showed a strong virtual inhibitory activity,the antiosteoarthritis effect of Fisetin may mainly act on TNF-αtarget.The modification of 3-hydroxyl group of Fisetin is the main structural modification

关 键 词：漆黄素 黄酮 骨关节炎 分子对接 结构修饰 

分 类 号：R914[医药卫生—药物化学]