[1]杨雪雨,赵腾腾,董珂珂,等.分子模拟研究多奈哌齐及其衍生物对AChE/BChE的抑制活性和选择性[J].南京师范大学学报(自然科学版),2017,40(03):123.[doi:10.3969/j.issn.1001-4616.2017.03.018]
　Yang Xueyu,Zhao Tengteng,Dong Keke,et al.Studies on the Bioactivity and Selectivity of Pyridonepezils to AChE/BChE by Molecular Modeling[J].Journal of Nanjing Normal University(Natural Science Edition),2017,40(03):123.[doi:10.3969/j.issn.1001-4616.2017.03.018]
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分子模拟研究多奈哌齐及其衍生物对AChE/BChE的抑制活性和选择性()
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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03期
页码:
123
栏目:
·化学·
出版日期:
2017-09-30

文章信息/Info

Title:
Studies on the Bioactivity and Selectivity of Pyridonepezils to AChE/BChE by Molecular Modeling
文章编号:
1001-4616(2017)03-0123-05
作者:
杨雪雨; 赵腾腾; 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 Xueyu; Zhao Tengteng; Dong Keke; 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:
胆碱酯酶; 多奈哌齐; 分子动力学模拟; MM-PBSA方法; 选择性
Keywords:
cholinesterase; donepezil; molecular dynamics simulation; MM-PBSA method; selectivity
分类号:
O643.1
DOI:
10.3969/j.issn.1001-4616.2017.03.018
文献标志码:
A
摘要:
乙酰胆碱酯酶(AChE)和丁酰胆碱酯酶(BChE)是具有高度同源的蛋白质,其在胆碱能神经系统中发挥着重要的作用. 在本文中,我们选取了已投入临床使用的药物多奈哌齐及其吡啶衍生物对AChE/BChE的抑制活性和选择性进行了研究. 我们采用MM-PBSA方法对两种抑制剂与AChE/BChE间的相互作用能进行了计算,结果表明范德华相互作用在总的结合能中贡献最大,且多奈哌齐的吡啶衍生物表现出比多奈哌齐更高的抑制活性以及选择性,所得计算结果与实验上抑制剂的抑制常数有较好的吻合.
Abstract:
Acetylcholinesterase(AChE)and butyrylcholinesterase(BChE)are highly homologous proteins and play important roles in the cholinergic nervous system. In current work,we investigate the bioactivity and selectivity of the pyridonepezils to AChE/BChE. The binding interactions between the two inhibitors and AChE/BChE are examined based on the MM-PBSA method. The results demonstrate that the van der Waals interactions have the largest contributions to the binding free energy,and the pyridonepezil exhibits higher bioactivity and selectivity to AChE/BChE compared to donepezil. The rank of calculated binding free energies is in good agreement with experimental inhibiting constants of the two inhibitors.

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相似文献/References:

[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(03):55.[doi:10.3969/j.issn.1001-4616.2018.01.011]

备注/Memo

备注/Memo:
收稿日期:2016-06-24.
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: 2017-09-30