[1]王亚莉,赵腾腾,朱小蕾.分子模拟研究AChE与酮类曼尼希碱衍生物抑制剂相互作用的结合机理[J].南京师范大学学报(自然科学版),2018,41(03):59.[doi:10.3969/j.issn.1001-4616.2018.03.010]
　Wang Yali,Zhao Tengteng,Zhu Xiaolei.Insights into the Binding of Ketone Mannich Base DerivativesInhibitors to AChE by Molecular Dynamics Simulation[J].Journal of Nanjing Normal University(Natural Science Edition),2018,41(03):59.[doi:10.3969/j.issn.1001-4616.2018.03.010]
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分子模拟研究AChE与酮类曼尼希碱衍生物抑制剂相互作用的结合机理()
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《南京师范大学学报》（自然科学版）[ISSN:1001-4616/CN:32-1239/N]

卷:
第41卷
期数:
2018年03期
页码:
59
栏目:
·化学·
出版日期:
2018-09-30

文章信息/Info

Title:
Insights into the Binding of Ketone Mannich Base DerivativesInhibitors to AChE by Molecular Dynamics Simulation
文章编号:
1001-4616(2018)03-0059-06
作者:
王亚莉; 赵腾腾; 朱小蕾
南京工业大学化工学院,材料化学工程国家重点实验室,江苏 南京 210009
Author(s):
Wang Yali; Zhao Tengteng; Zhu Xiaolei
State Key Laboratory of Materials-Oriented Chemical Engineering,College of Chemistry and Chemical Engineering,Nanjing University of Technology,Nanjing 210009,China
关键词:
酮类曼尼希碱衍生物抑制剂; 乙酰胆碱酯酶; 分子动力学模拟; 结合自由能
Keywords:
ketone Mannich base derivatives inhibitors; AChE; molecular dynamics simulation; binding free energy
分类号:
O643.1
DOI:
10.3969/j.issn.1001-4616.2018.03.010
文献标志码:
A
摘要:
主要通过分子对接(autodock)、分子动力学(MD)模拟和结合自由能(MM/PBSA)计算等方法研究了3种酮类曼尼希碱衍生物抑制剂(下文它们被标记为M1、M2和M3)与AChE的结合模式和相互作用机理. 分析表明,结合自由能的计算结果与实验测得的IC50值结果相对应,而范德华相互作用是这3种抑制剂与AChE结合的主要驱动力. 其中,M2和M3与AChE的结合模式相似,但与M1相比有些不同,这点在抑制剂与周围残基之间的能量分析上也有所体现. 残基W84和E82则是区分抑制剂M1、M2和M3生物活性高低的关键性残基.
Abstract:
We investigate the binding mode and the interaction mechanism of three ketone Mannich base derivative inhibitors(they are marked as M1,M2,and M3 hereunder)with AChE in terms of molecular docking(autodock),molecular dynamics simulation(MD)and binding free energy calculation(MM/PBSA)methods. The results of binding free energy correspond to the experimental bioactivity data(IC50 values)of three inhibitors. The Van der Waals interaction is the main driving force in binding affinity of the three inhibitors with AChE. Although the binding modes of M2 and M3 are similar,they are different from that of M1/AChE,which are reflected in the energy analysis between the three inhibitors and the surrounding residues. Residues W84 and E82 are the key residues that can distinguish the bioactivity of M1,M2 and M3,respectively.

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备注/Memo

备注/Memo:
收稿日期:2018-04-04.
基金项目:国家自然科学基金项目(20706029、20876073、91434109).
通讯联系人:朱小蕾,博士,教授,研究方向:分子模拟的研究工作. E-mail:xlzhu@njtech.edu.cn
更新日期/Last Update: 2018-11-19