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[1]董珂珂,王璇,杨雪雨,等.基于蛋白质专一性力场和分子动力学模拟研究细胞周期依赖性蛋白激酶5与Roscovitine衍生物的作用机制[J].南京工业大学学报(自然科学版),2017,39(02):127-132.[doi:10.3969/j.issn.1671-7627.2017.02.021]
 DONG Keke,WANG Xuan,YANG Xueyu,et al.Mechanism of roscovitine derivatives with CDK5 using polarized protein-specific force field and molecular dynamics simulations[J].Journal of NANJING TECH UNIVERSITY(NATURAL SCIENCE EDITION),2017,39(02):127-132.[doi:10.3969/j.issn.1671-7627.2017.02.021]
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基于蛋白质专一性力场和分子动力学模拟研究细胞周期依赖性蛋白激酶5与Roscovitine衍生物的作用机制()
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《南京工业大学学报(自然科学版)》[ISSN:1671-7627/CN:32-1670/N]

卷:
39
期数:
2017年02期
页码:
127-132
栏目:
出版日期:
2017-03-20

文章信息/Info

Title:
Mechanism of roscovitine derivatives with CDK5 using polarized protein-specific force field and molecular dynamics simulations
文章编号:
1671-7627(2017)02-0127-06
作者:
董珂珂王璇杨雪雨朱小蕾
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):
DONG Keke WANG Xuan YANG Xueyu ZHU Xiaolei
State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Nanjing Tech University, Nanjing 210009, China
关键词:
Roscovitine衍生物 细胞周期依赖性蛋白激酶5 分子动力学模拟 蛋白质专一性电荷
Keywords:
roscovitine derivatives CDK5 molecular dynamics simulation PPC
分类号:
O643.1
DOI:
10.3969/j.issn.1671-7627.2017.02.021
文献标志码:
A
摘要:
本文通过分子对接,将极化的蛋白质专一性电荷(PPC)替换AMBERFF03电荷,利用分子动力学模拟(MD)和结合自由能计算等方法研究3种Roscovitine衍生物抑制剂与细胞周期依赖性蛋白激酶5(CDK5)的相互作用,分析药物与其周围残基之间的氢键作用以及蛋白质极化对静电作用和范德华作用等的影响。模拟结果表明:3种抑制剂与CDK5的结合模式很相似,范德华力对亲和能有较大贡献。但残基分解分析表明Glu81、Cys83和Lys89与抑制剂形成静电相互作用能显著区分3种不同Roscovitine衍生物类抑制剂的生物活性。
Abstract:
Molecular docking, molecular dynamics(MD)simulations with substituting the standard AMBERFF03 force field using the polarized protein specific charge(PPC), and binding free energy analysis were performed to investigate the interaction between three roscovitine derivatives and cyclin-dependent kinase 5(CDK5). The hydrogen bonding interactions between three inhibitors and adjacent residues and the effect of polarization on electrostatic and van der Waals interactions were analyzed and discussed. Results showed that the binding modes of 3 inhibitors were similar with a great contribution of van der Waals interaction on affinity. The energy decomposition analysis indicated that Glu81, Cys83 and Lys89 are the key residues for differentiating the bioactivity of three inhibitors.

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备注/Memo

备注/Memo:
收稿日期:2015-10-23
基金项目:国家自然科学基金(20706029, 20876073, 91434109)
作者简介:董珂珂(1989—),女,河南滑县人,博士,主要研究方向为分子模拟; 朱小蕾(联系人),教授,E-mail:xlzhu@njtech.edu.cn.
引用本文:董珂珂,王璇,杨雪雨,等.基于蛋白质专一性力场和分子动力学模拟研究细胞周期依赖性蛋白激酶5与Roscovitine衍生物的作用机制[J].南京工业大学学报(自然科学版),2017,39(2):127-132..
更新日期/Last Update: 2017-03-20