| 人类胞外信号调节激酶1的同源模建及其抑制剂的对接与结构改造 |
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| 引用本文： | 张继龙,侯瑞哲,李卓,郑清川,张红星. 人类胞外信号调节激酶1的同源模建及其抑制剂的对接与结构改造[J]. 化学学报, 2010, 68(3): 222-226 |
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| 作者姓名： | 张继龙 侯瑞哲 李卓 郑清川 张红星 |
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| 作者单位： | 吉林大学理论化学研究所理论化学计算国家重点实验室,长春,130023;吉林大学白求恩医学院,长春,130021 |
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| 基金项目： | 国家自然科学基金(No20903045,20573042);;国家科技支撑计划重点项目(No2006BAE03B01);;高等学校博士点学科专项基金(No20070183046);;吉林大学基本科研业务费(No200810018)资助项目 |
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| 摘 要： | 通过同源模建和分子动力学模拟构建了人类胞外信号调节激酶1(hERK1)的三维结构,并利用profile-3D和procheck方法评估了模型的合理性.对所得的结构使用分子对接程序Affinity和CDOCKER进行了两种抑制剂的对接.结果显示这两种抑制剂与酶的结合方式相似,它们均与残基K36,Q87之间存在氢键作用,二者取代基的不同导致了抑制能力的差别.基于对接结果分析,对已知抑制剂进行结构改造,得到了一个理论上结合能力更强的抑制剂.它在保持与K36和Q87之间氢键的同时,又与残基D93,K96,S135形成了四条氢键,显著提高了与酶的相互作用.对接相互作用能显著下降,MM-PBSA结合自由能降为负值,这些均体现了抑制能力的提高.本工作对于针对该酶的抑制剂设计和相关疾病的新药开发具有理论指导价值.
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| 关 键 词： | 人类胞外信号调节激酶1 同源模建 分子动力学 对接 抑制剂 |
| 收稿时间： | 2009-08-14 |
| 修稿时间： | 2009-10-23 |
Homology Modeling of Human Extracellular Signal-regulated Kinase 1 and Docking and Reconstitution of Its Inhibitors |
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| Zhang Jilong,Hou Ruizhe,Li Zhuo,Zheng Qingchuan,Zhang Hongxing. Homology Modeling of Human Extracellular Signal-regulated Kinase 1 and Docking and Reconstitution of Its Inhibitors[J]. Acta Chimica Sinica, 2010, 68(3): 222-226 |
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| Authors: | Zhang Jilong Hou Ruizhe Li Zhuo Zheng Qingchuan Zhang Hongxing |
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| Affiliation: | a State Key Laboratory of Theoretical and Computational Chemistry;Institute of Theoretical Chemistry;Jilin University;Changchun 130023;b Norman Bethune College of Medicine;Changchun 130021 |
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| Abstract: | The three dimensional structure of human extracellular signal-regulated kinase 1(hERK1) was modeled and refined using homology modeling and molecular dynamics simulation.The model was assessed by profile-3D and procheck methods,which confirmed that the obtained model was reliable.Two inhibitors were docked into the refined structure by the molecular docking programs,Affinity and CDOCKER.The results show that the two inhibitors share the similar binding pattern,which interact with the residues K36 and Q87 by... |
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| Keywords: | hERK1 homology modeling molecular dynamics molecular docking inhibitors |
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