[1]赵腾腾,杨雪雨,王亚莉,等.分子模拟研究1,3,4-噻二唑类衍生物对AChE/BChE的生物活性和选择性机理[J].南京师范大学学报(自然科学版),2018,41(01):55.[doi:10.3969/j.issn.1001-4616.2018.01.011]
　Zhao Tengteng,Yang Xueyu,Wang Yali,et al.Studies on Mechanism of Bioactivity and Selectivity of 1,3,4-ThiadiazolInhibitors to AChE/BChE by Molecular Dynamic[J].Journal of Nanjing Normal University(Natural Science Edition),2018,41(01):55.[doi:10.3969/j.issn.1001-4616.2018.01.011]
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分子模拟研究1,3,4-噻二唑类衍生物对AChE/BChE的生物活性和选择性机理()
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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01期
页码:
55
栏目:
·化学·
出版日期:
2018-03-31

文章信息/Info

Title:
Studies on Mechanism of Bioactivity and Selectivity of 1,3,4-ThiadiazolInhibitors to AChE/BChE by Molecular Dynamic
文章编号:
1001-4616(2018)01-0055-06
作者:
赵腾腾; 杨雪雨; 王亚莉; 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):
Zhao Tengteng; Yang Xueyu; Wang Yali; Zhu Xiaolei
State Key Laboratory of Materials-Oriented Chemical Engineering,College of Chemical Engineering,Nanjing Tech University,Nanjing 210009,China
关键词:
胆碱酯酶; 1; 3; 4-噻二唑类抑制剂; 分子动力学模拟; MM-PBSA方法; 选择性
Keywords:
cholinesterase; 1; 3; 4-thiadiazol inhibitors; molecular dynamics simulation; MM-PBSA method; selectivity
分类号:
O643.1
DOI:
10.3969/j.issn.1001-4616.2018.01.011
文献标志码:
A
摘要:
乙酰胆碱酯酶(AChE)和丁酰胆碱酯酶(BChE)均属于胆碱酯酶类(ChEs),具有不同的催化特性及抑制模式,是具有高度同源性的两种蛋白质,在神经系统中发挥着重要的作用. 揭示胆碱酯酶抑制剂的选择性机理是开发新型的阿尔茨海默症药物的重要课题. 我们研究了3种1,3,4-噻二唑抑制剂对AChE/BChE的生物活性和选择性机理. 采用MM-PBSA方法对3种抑制剂与AChE/BChE之间的相互作用能进行了计算. 研究结果表明,3种抑制剂对AChE均表现出较高的活性,说明这3种抑制剂能够选择性抑制AChE,所得
Abstract:
Acetylcholinesterase(AChE)and butyrylcholinesterase(BChE)both belonging to the family of cholinesterases(ChEs),which differ in their catalytic properties and inhibition patterns,are highly homologous proteins and play important roles in the cholinergic nervous system. Revealing selectivity mechanism of inhibitors to cholinesterases is an important issue to develop potential Alzheimer’s drugs. In current work,we investigate the bioactivity and selectivity of three 1,3,4-thiadiazol inhibitors to AChE/BChE. The binding interactions between the three inhibitors and AChE/BChE are examined based on the MM-PBSA method. The results demonstrate that three kinds of inhibitors show higher activity to AChE than BChE,and illustrate that the three inhibitors can inhibit AChE selectively. The rank of calculated binding free energies is in good agreement with experimental inhibiting constants of the three inhibitors.

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备注/Memo

备注/Memo:
收稿日期:2017-03-22.
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: 2018-03-31