[1]杨雪雨,王 璇,董珂珂,等.乙酰胆碱酯酶AChE与其抑制剂1,3,4-噻二唑类衍生物的结合机理研究[J].南京师范大学学报(自然科学版),2017,40(02):144.[doi:10.3969/j.issn.1001-4616.2017.02.024]
 Yang Xueyu,Wang Xuan,Dong Keke,et al.Investigation of Binding Mechanism Between 1,3,4-ThiadiazolInhibitors and AChE by Molecular Dynamic Simulations[J].Journal of Nanjing Normal University(Natural Science Edition),2017,40(02):144.[doi:10.3969/j.issn.1001-4616.2017.02.024]
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乙酰胆碱酯酶AChE与其抑制剂1,3,4-噻二唑类衍生物的结合机理研究()
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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40卷
期数:
2017年02期
页码:
144
栏目:
·化学·
出版日期:
2017-06-29

文章信息/Info

Title:
Investigation of Binding Mechanism Between 1,3,4-ThiadiazolInhibitors and AChE by Molecular Dynamic Simulations
文章编号:
1001-4616(2017)02-0144-05
作者:
杨雪雨王 璇董珂珂朱小蕾
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):
Yang XueyuWang XuanDong KekeZhu Xiaolei
State Key Laboratory of Materials-Oriented Chemical Engineering,College of Chemistryand Chemical Engineering,Nanjing University of Technology,Nanjing 210009,China
关键词:
阿尔茨海默病乙酰胆碱酯酶134噻二唑类抑制剂分子模拟MM-PBSA
Keywords:
Alzheimer’s diseaseAChE134-thiadiazol inhibitorsmolecular simulationMM-PBSA
分类号:
O643.1
DOI:
10.3969/j.issn.1001-4616.2017.02.024
文献标志码:
A
摘要:
阿尔茨海默病(Alzheimer’s disease,AD)是老年痴呆的一种,在老年人中有较高的发病率,乙酰胆碱酯酶抑制剂(AChEI)是目前广泛应用于临床治疗这类病症的主要药物. 我们选择3种1,3,4-噻二唑抑制剂,分别与AChE进行分子对接和分子动力学(MD)模拟研究其结合模式以及相互作用机理. 通过MM-PBSA方法分别计算了3种抑制剂与酶之间的自由结合能,计算结果与实验中测得的抑制剂的IC50值相一致. 抑制剂与周围残基之间的氢键作用以及能量分析合理解释了AChE与抑制剂之间的结合模式以及相互作用机理.
Abstract:
Alzheimer’s disease(AD),one form of dementia,is the disease of high incidence among the elderly. The acetylcholinesterase inhibitors(AChEI)are main drugs of treating AD,which are widely used in clinical application. We use molecular docking and molecular dynamics(MD)simulations to investigate the binding mode and interaction mechanism between three 1,3,4-thiadiazol inhibitors and AChE. The binding free energies are calculated based on MM-PBSA method. The ranking of binding free energies is consistent with that of the experimental IC50 values. The hydrogen-bond interaction between the inhibitor and the residues as well as the energy analysis reasonably explained the binding mode and the interaction mechanism between AChE and the inhibitors.

参考文献/References:

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备注/Memo

备注/Memo:
收稿日期:2016-03-28.
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. E-mail:xlzhu@njtech.edu.cn
更新日期/Last Update: 2017-06-30