UNDERSTANDING THE MOLECULAR MECHANISM OF BINDING MODES OF AURORA A INHIBITORS BY LONG TIME SCALE GPU DYNAMICS
文献类型：期刊论文
| 作者 | Fu, Ting1,2,3; Wu, Xue1,2,3; Xiu, Zhilong1; Wang, Jinguang4; Yin, Liu5; Li, Guohui2 |
| 刊名 | journal of theoretical & computational chemistry
 |
| 出版日期 | 2013-12-01 |
| 卷号 | 12期号:8页码:1341003 |
| 关键词 | Aurora A molecular dynamics simulations MM-PB/GBSA |
| 产权排序 | 待补充 |
| 通讯作者 | 李国辉 |
| 合作状况 | 英 |
| 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. |
| WOS标题词 | science & technology ; physical sciences |
| 学科主题 | 物理化学 |
| 类目[WOS] | chemistry, multidisciplinary |
| 研究领域[WOS] | chemistry |
| 关键词[WOS] | continuum solvent models ; free-energy calculations ; kinase inhibitors ; diverse set ; simulations ; combination ; activation ; discovery ; proteins ; hydrogen |
| 收录类别 | SCI |
| 资助信息 | 2，1 |
| 原文出处 | 1341003 |
| 语种 | 英语 |
| WOS记录号 | WOS:000328359500003 |
| 公开日期 | 2014-09-11 |
| 源URL | [http://159.226.238.44/handle/321008/119437]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 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 |
| 推荐引用方式 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,&Li, Guohui.(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. |
入库方式： OAI收割
来源：大连化学物理研究所
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