葛根素与乙酰胆碱酯酶作用的分子动力学模拟  

Molecular dynamics simulation of the interactions between puerarin and acetylcholinesterase

作　　者：赵奇 邓培渊 王会鱼 罗青 田云芳 王国霞 杨玉珍 李春阁 陈刚 ZHAO Qi;DENG Pei-Yuan;WANG Hu-Yu;LUO Qing;TIAN Yun-Fang;WANG Guo-Xia;YANG Yu-Zhen;LI Chun-Ge;CHEN Gang(School of Life Science,Zhengzhou Normal University,Zhengzhou 450044,China)

机构地区：[1]郑州师范学院生命科学学院,郑州450044

出　　处：《原子与分子物理学报》2022年第6期21-27,共7页Journal of Atomic and Molecular Physics

基　　金：郑州师范学院本科教学改革项目(JXGG-20772);郑州师范学院线上线下混合式-流课程建设项目(XSXXHHSYLKC 211465);教育部人文社科青年基金项目(19JYCZH263)。

摘　　要：旨在阐明葛根素与乙酰胆碱酯酶(AChE)的分子作用机制,并为基于葛根素的类似物的AChE抑制剂的研发提供参考.运用AutoDock 4.2进行葛根素与AChE的分子对接,采用YASARA进行分子动力学模拟,利用MMPBSA.py模块计算复合体系的结合自由能,分析氨基酸的能量贡献.结果显示,葛根素与AChE对接体系含有4个氢键,2个π-π键.5 ns后,体系均方根偏差(RMSD)趋于平衡,体系结合自由能为-18.19 kcal/mol.促体系结合的主要作用力是范德华力、静电作用力,非溶剂化能是主要的结合阻力.能量贡献最大的残基依次为Asn533、Lys530、Ala534、Pro529.这些研究为新型抑制剂的研发提供理论参考.This study was performed to illustrate the molecular mechanism of Puerarin and Acetylcholinesterase(AChE),and provide reference for AChE inhibitors research based on puerarin analogs.AutoDock 4.2 was used to dock Puerarin and AChE.Molecular dynamics simulation was conducted by YASARA platform,binding free energy of the composite system was calculated with MMPBSA.py,and the energy contribution of amino acids was analyzed.The results showed that the complex of Puerarin and AChE contains 4 hydrogen bonds,2π-πkeys.Root mean square deviation(RMSD)of the complex tends to balance after 5 ns.Binding free energy of the composite system is-18.19 kcal/mol.The main driving force are the van der Waals and electrostatic forces,While the main resistance force come from nonpolar solvation energy.The residues of largest energy contribution are Asn533,Lys530,Ala534 and Pro529.These data provide the theoretical fundamental for further exploitations of efficient AChE inhibitors of puerarin analogues.

关 键 词：阿尔茨海默症 乙酰胆碱酯酶 葛根素 分子动力学 结合自由能 

分 类 号：O64[理学—物理化学]