DICP OpenIR
Subject Area物理化学
UNDERSTANDING THE MOLECULAR MECHANISM OF BINDING MODES OF AURORA A INHIBITORS BY LONG TIME SCALE GPU DYNAMICS
Fu, Ting1,2,3; Wu, Xue1,2,3; Xiu, Zhilong1; Wang, Jinguang4; Yin, Liu5; Li, Guohui2; Li GH(李国辉)
KeywordAurora a Molecular Dynamics Simulations Mm-pb/gbsa
Source PublicationJOURNAL OF THEORETICAL & COMPUTATIONAL CHEMISTRY
2013-12-01
DOI10.1142/S0219633613410034
Volume12Issue:8Pages:1341003
Indexed BySCI
Cooperation Status
SubtypeArticle
Department11
Funding Project1106
Contribution Rank待补充
WOS HeadingsScience & Technology ; Physical Sciences
Funding Organization2,1 ; 2,1 ; 2,1 ; 2,1
WOS SubjectChemistry, Multidisciplinary
WOS Research AreaChemistry
WOS KeywordCONTINUUM SOLVENT MODELS ; FREE-ENERGY CALCULATIONS ; KINASE INHIBITORS ; DIVERSE SET ; SIMULATIONS ; COMBINATION ; ACTIVATION ; DISCOVERY ; PROTEINS ; HYDROGEN
AbstractInhibition 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.
Language英语
Funding Organization2,1 ; 2,1 ; 2,1 ; 2,1
URL查看原文
WOS IDWOS:000328359500003
Citation statistics
Cited Times:5[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/119437
Collection中国科学院大连化学物理研究所
Corresponding AuthorLi GH(李国辉)
Affiliation1.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
GB/T 7714
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.
APA Fu, Ting.,Wu, Xue.,Xiu, Zhilong.,Wang, Jinguang.,Yin, Liu.,...&李国辉.(2013).UNDERSTANDING THE MOLECULAR MECHANISM OF BINDING MODES OF AURORA A INHIBITORS BY LONG TIME SCALE GPU DYNAMICS.JOURNAL OF THEORETICAL & COMPUTATIONAL CHEMISTRY,12(8),1341003.
MLA Fu, Ting,et al."UNDERSTANDING THE MOLECULAR MECHANISM OF BINDING MODES OF AURORA A INHIBITORS BY LONG TIME SCALE GPU DYNAMICS".JOURNAL OF THEORETICAL & COMPUTATIONAL CHEMISTRY 12.8(2013):1341003.
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