[1]王　璇,杨雪雨,董珂珂,等.三氢-咪唑并［4，5-c］喹啉-4（5H）-酮衍生物与二肽基肽酶-4结合机理的理论研究[J].南京师范大学学报(自然科学版),2016,39(03):62.[doi:10.3969/j.issn.1001-4616.2016.03.011]
　Wang Xuan,Yang Xueyu,Dong Keke,et al.A Study on Binding Mechanism of 3H-imidazo［4，5-c］quinolin-4（5H）-onesto Dipeptidyl Peptidase IV Based on Molecular Dynamics Simulation[J].Journal of Nanjing Normal University(Natural Science Edition),2016,39(03):62.[doi:10.3969/j.issn.1001-4616.2016.03.011]
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三氢-咪唑并［4，5-c］喹啉-4（5H）-酮衍生物与二肽基肽酶-4结合机理的理论研究()
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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39卷
期数:
2016年03期
页码:
62
栏目:
·化学·
出版日期:
2016-09-30

文章信息/Info

Title:
A Study on Binding Mechanism of 3H-imidazo［4，5-c］quinolin-4（5H）-onesto Dipeptidyl Peptidase IV Based on Molecular Dynamics Simulation
文章编号:
1001-4616（2016）03-0062-05
作者:
王　璇; 杨雪雨; 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):
Wang Xuan; Yang Xueyu; 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:
分子动力学模拟; MM-PBSA; 二肽基肽酶; 三氢-咪唑并［4; 5-c］喹啉-4（5H）-酮衍生物抑制剂
Keywords:
molecular dynamics simulation; MM-PBSA; DPP-4; 3H-imidazo［4; 5-c］quinolin-4（5H）-ones
分类号:
O643.1
DOI:
10.3969/j.issn.1001-4616.2016.03.011
文献标志码:
A
摘要:
通过分子对接、分子动力学（MD）模拟和结合自由能分析的方法研究了三氢-咪唑并［4，5-c］喹啉-4（5H）-酮衍生物药物与二肽基肽酶之间的成键机制，分析和讨论了抑制剂和相邻残基之间的氢键和疏水相互作用. 用MM-PBSA方法计算得到的4个抑制剂的结合自由能与实验上测得的结果是一致的. 抑制剂与DPP-4的关键残基间的范德华相互作用对于体系的结合能有较大的贡献，并且是区分不同抑制剂生物活性的标志之一.
Abstract:
We apply molecular docking，molecular dynamics（MD）simulations and binding free energy analysis to investigate and reveal the binding mechanism between four 3H-imidazo［4，5-c］quinolin-4（5H）-ones and DPP-4. The hydrogen bonding and hydrophobic interactions between inhibitors and adjacent residues are analyzed and discussed. The calculated binding free energies using MM-PBSA method are consistent with the experimental data. The van der Waals interaction between key residues of DPP-4 and inhibitors has larger contribution to total energy and can distinguish the binding affinity of four inhibitors.

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备注/Memo

备注/Memo:
收稿日期：2015-10-29.　
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: 2016-09-30