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学科主题: 物理化学
题名: UNDERSTANDING THE MOLECULAR MECHANISM OF BINDING MODES OF AURORA A INHIBITORS BY LONG TIME SCALE GPU DYNAMICS
作者: Fu, Ting1, 2, 3;  Wu, Xue1, 2, 3;  Xiu, Zhilong1;  Wang, Jinguang4;  Yin, Liu5;  Li, Guohui2
通讯作者: 李国辉
关键词: Aurora A ;  molecular dynamics simulations ;  MM-PB/GBSA
刊名: JOURNAL OF THEORETICAL & COMPUTATIONAL CHEMISTRY
发表日期: 2013-12-01
DOI: 10.1142/S0219633613410034
卷: 12, 期:8, 页:1341003
收录类别: SCI
合作性质: 
文章类型: Article
部门归属: 11
项目归属: 1106
产权排名: 待补充
WOS标题词: Science & Technology ;  Physical Sciences
类目[WOS]: Chemistry, Multidisciplinary
资助者: 2,1
研究领域[WOS]: Chemistry
英文摘要: Inhibition of Aurora A kinase interaction is considered to be a promising approach for the discovery of new molecularly targeted cancer therapeutics. In this study, the binding mechanisms of two different inhibitors with a contrasting binding affinity to Aurora A were investigated by long time scale GPU molecular dynamics (MD) simulations coupled with molecular mechanics-Poisson-Boltzmann/generalized Born surface area (MM-PB/GBSA) method. The results showed that the predicted binding free energies of these two complexes were consistent with the experimental data. Through analyzing the individual energy components of binding free energy, we found that the van der Waals contribution was the main force to drive the inhibitor-protein binding and the electrostatic contribution was also a crucial factor for the inhibitor-Aurora A binding. The structural analysis demonstrated that the inhibitor HPM could produce more hydrophobic interaction contacts with Aurora A than that of 2JZ, and the loss of key hydrogen bonds between the inhibitor and residue Arg137 in the hinge region of Aurora A was another important reason for the weaker binding affinity of 2JZ to Aurora A. This study sheds more light on the development of the efficient inhibitors targeting the Aurora A.
关键词[WOS]: CONTINUUM SOLVENT MODELS ;  FREE-ENERGY CALCULATIONS ;  KINASE INHIBITORS ;  DIVERSE SET ;  SIMULATIONS ;  COMBINATION ;  ACTIVATION ;  DISCOVERY ;  PROTEINS ;  HYDROGEN
语种: 英语
原文出处: 查看原文
WOS记录号: WOS:000328359500003
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/119437
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Dalian Univ Technol, Dept Biosci & Biotechnol, Sch Environm & Biol Sci & Technol, Dalian 116024, Peoples R China
2.Chinese Acad Sci, Lab Mol Modeling & Design, State Key Lab Mol React Dynam, Dalian Inst Chem Phys, Dalian 116023, Peoples R China
3.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China
4.Dalian Med Univ, Affiliated Hosp 1, Dept Thorac Surg, Dalian 116011, Liaoning Provin, Peoples R China
5.Dalian Med Univ, Affiliated Hosp 1, Dept Oncol, Dalian 116011, Liaoning Provin, Peoples R China

Recommended Citation:
Fu, Ting,Wu, Xue,Xiu, Zhilong,et al. UNDERSTANDING THE MOLECULAR MECHANISM OF BINDING MODES OF AURORA A INHIBITORS BY LONG TIME SCALE GPU DYNAMICS[J]. JOURNAL OF THEORETICAL & COMPUTATIONAL CHEMISTRY,2013,12(8):1341003.
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