化学化工学院机构知识库

Institutional Repository, College of Chemistry and Chemical Engineering

 

兰州大学机构库  > 化学化工学院  > 期刊论文
题名: Computational study on the binding and unbinding mechanism of HCV NS5B with the inhibitor GS-461203 and substrate using conventional and steered molecular dynamics simulations
作者: Pan, DB; Niu, YZ; Ning, LL; Zhang, Y; Liu, HX; Yao, XJ(姚小军)
收录类别: SCIE
出版日期: 2016-08-15
刊名: CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS
卷号: 156, 页码:72-80
英文摘要: The active metabolite GS-461203 of hepatitis C virus (HCV) non-structural protein 5B (NS5B) inhibitor sofosbuvir can stall RNA synthesis or replication by competitively inhibiting the natural substrate nucleoside triphosphate like UTP. Unfortunately, S282T mutant can lead to the resistance to sofosbuvir. Here, the detailed binding mechanism and unbinding process of GS-461203 and UTP to HCV NS5B were unraveled by using conventional molecular dynamics (MD) simulation and steered molecular dynamics (SMD) simulation. Our simulation results demonstrate that both polar and nonpolar interactions are favorable for GS-461203 and UTP binding. Meanwhile, we also identified the key residues responsible for GS-461203 and UTP binding in NS5B-RNA together with the three unbinding process steps including translation, reversal of base and ribose and complete divorce. The 2'-fluoro-2'-C-methyl ribose of GS-461203 can form stronger polar and nonpolar interactions with residues S282 and 1160 than UTP. The results can also explain the reason why GS-461203 can effectively be incorporated into RNA synthesis or replication. In the S282T mutant system, the binding affinity attenuation of UTP relative to wild type HCV NS5B is less than that of GS-461203. The obtained binding and unbinding mechanism of HCV NS5B with the inhibitor GS-461203 and substrate in our work will provide useful guidance for the development of new and effective HCV NS5B inhibitors with low resistance. (C) 2016 Elsevier B.V. All rights reserved.
关键词: Hepatitis C Virus NS5B RNA-dependent RNA polymerase ; GS-461203 ; Molecular dynamics simulation ; Binding free energy calculations
作者部门: [Pan, Dabo ; Niu, Yuzhen ; Ning, Lulu ; Yao, Xiaojun] Lanzhou Univ, Dept Chem, State Key Lab Appl Organ Chem, Lanzhou 730000, Peoples R China ; [Zhang, Yang] Lanzhou Univ, Sch Informat Sci & Engn, Lanzhou 730000, Peoples R China ; [Liu, Huanxiang] Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China
通讯作者: Liu, HX (reprint author), Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China. ; Yao, XJ (reprint author), Lanzhou Univ, Dept Chem, Lanzhou 730000, Peoples R China.
学科分类: Automation & Control Systems; Chemistry; Computer Science; Instruments & Instrumentation; Mathematics
文章类型: Article
所属项目编号: National Natural Science Foundation of China [21475054] ; Fundamental Research Funds for the Central Universities [lzujbky-2014-191]
所属项目名称: 国家自然科学基金项目 ; 中央高校基本科研业务费专项资金
项目资助者: NSFC ; LZU
语种: 英语
DOI: 10.1016/j.chemolab.2016.05.015
ISSN号: 0169-7439
WOS记录号: WOS:000380415100008
IR记录号: WOS:000380415100008
第一机构:
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.lzu.edu.cn/handle/262010/180541
Appears in Collections:化学化工学院_期刊论文

Files in This Item:

There are no files associated with this item.


Recommended Citation:
Pan, DB,Niu, YZ,Ning, LL,et al. Computational study on the binding and unbinding mechanism of HCV NS5B with the inhibitor GS-461203 and substrate using conventional and steered molecular dynamics simulations[J]. CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS,2016,156:72-80.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Altmetrics Score
 
Google Scholar
Similar articles in Google Scholar
[Pan, DB]'s Articles
[Niu, YZ]'s Articles
[Ning, LL]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Pan, DB]‘s Articles
[Niu, YZ]‘s Articles
[Ning, LL]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Email:
Passwd
验 证:
换一张
Have you forgotten your password? Log In
Copyright © 2007-2017  兰州大学 - Feedback
Powered by CSpace