基于分子对接与分子动力学模拟探讨生慧颗粒有效成分对γ氨基丁酸A型受体与乙酰胆碱酯酶的作用机制  

Discussion on the mechanism of Shenghui Granule acting on GABAaR and AChE based on molecular docking and molecular dynamics simulation

作　　者：李泽飞 王平 LI Zefei;WANG Ping(School of Basic Medicine,Hubei University of Chinese Medicine,Wuhan 430065,China;School of Medicine,Jianghan University,Wuhan 430056,China)

机构地区：[1]湖北中医药大学基础医学院,武汉430065 [2]江汉大学医学部,武汉430056

出　　处：《中华中医药杂志》2024年第1期157-162,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金重点项目(No.82130119);教育部工程研究中心建设项目(No.202234)。

摘　　要：目的:使用分子对接与分子动力学模拟研究生慧颗粒有效成分对γ氨基丁酸A型受体(GABAaR)与乙酰胆碱酯酶(AChE)作用机制。方法:收集生慧颗粒有效成分,使用LibDock将所有成分分别与GABAaR与AChE进行对接并分析作用残基。对最佳结合构象进行30 ns分子动力学模拟,分析结合稳定性及结合能。结果:收集到生慧颗粒有效成分26个。分子对接表明优于地西泮(DZP)成分18个,最优成分为Acteoside。优于多奈哌齐(DNPQ)成分4个,最优成分为PolygalaxanthoneⅢ。分子动力学模拟表明GABAaR与Acteoside可稳定结合,结合能为(-29.60±3.53)kcal/mol。PolygalaxanthoneⅢ在7 ns前与AChE稳定结合,之后脱离结合位点,在27~27.5 ns再次进入结合位点,其结合能在4~6 ns与27~27.5 ns分别为(-14.12±3.03)kcal/mol、(-8.16±2.95)kcal/mol。结论:生慧颗粒治疗失眠和AD的潜在物质基础分别为Acteoside、PolygalaxanthoneⅢ。Objective:Using molecular docking and molecular dynamics simulation to study the mechanism of action of active ingredients of Shenghui Granule onγ-aminobutyric acid type A receptor(GABAaR)and acetylcholinesterase(AChE).Methods:Collect the active ingredients of Shenghui Granule.All components were docked with GABAaR and AChE respectively by using LibDock,followed by analysis of interacting residues.Perform 30 ns molecular dynamics simulation on the best binding conformation to analyze binding stability and binding energy.Results:A total of 26 active ingredients of Shenghui Granules were collected.Molecular docking showed that there were 18 components superior to diazepam(DZP),and the best component was Acteoside.There were 4 components superior to donepezil(DNPQ),and the best component was Polygalaxanthone III.Molecular dynamics simulations showed that GABAaR could be stably combined with Acteoside,and the binding energy was(-29.60±3.53)kcal/mol.Polygalaxanthone III could be stably combined with AChE stably for 7 ns,then breaks away from the binding site,and re-entered in the binding site at 27-27.5 ns,and its binding energy was(-14.12±3.03)kcal/mol at 4-6 ns and(-8.16±2.95)kcal/mol at 27-27.5 ns,respectively.Conclusion:The potential ingredients of Shenghui Granules in treating insomnia and AD are Acteoside and Polygalaxanthone III,respectively.

关 键 词：生慧颗粒 分子对接 分子动力学模拟 γ氨基丁酸A型受体 乙酰胆碱酯酶 

分 类 号：R285[医药卫生—中药学]