物理化学学报 >> 2005, Vol. 21 >> Issue (11): 1229-1234.doi: 10.3866/PKU.WHXB20051107

研究论文 上一篇    下一篇

用分子模拟方法研究HIV-1整合酶与咖啡酰基类抑制剂的相互作用

刘春莉; 李春华; 陈慰祖; 王存新   

  1. 北京工业大学生命科学与生物工程学院, 北京100022
  • 收稿日期:2005-04-04 修回日期:2005-05-23 发布日期:2005-11-15
  • 通讯作者: 王存新 E-mail:cxwang@bjut.edu.cn

Study on Interaction between HIV-1 Integrase and Its Dicaffeoyl Inhibitors through Molecular Modeling Approach

LIU Chun-li; LI Chun-hua; CHEN Wei-zu; WANG Cun-xin   

  1. College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100022
  • Received:2005-04-04 Revised:2005-05-23 Published:2005-11-15
  • Contact: WANG Cun-xin E-mail:cxwang@bjut.edu.cn

摘要: 用分子对接和分子动力学(MD)模拟方法研究了一类咖啡酰基和没食子酰基类HIV-1整合酶抑制剂与整合酶之间的相互作用模式, 结果表明该类抑制剂分子上的两个侧链基团(咖啡酰基或没食子酰基)与整合酶的DDE基序之间的相互作用对抑制整合酶活性起到关键作用. 当侧链基团为没食子酰基时, 可以提高该类抑制剂与整合酶的结合能力. 采用线性相互作用能方法(LIE)计算了该类抑制剂与整合酶之间的结合自由能, 预测值与实验值相吻合, 均方根偏差RMSD为1.39 kJ•mol-1, 以上结果可为基于结构的HIV-1整合酶抑制剂设计提供有用的信息.

关键词: HIV-1整合酶抑制剂, 整合酶, 分子动力学模拟, 咖啡酰基, 没食子酰基

Abstract: The binding mode of a series of dicaffeoyl or digalloyl pyrrolidine and furan derivatives inhibitors with HIV-1 integrase was proposed by using molecular docking and molecular dynamics (MD) simulation methods. The results indicate that the interactions between HIV-1 integrase conserved DDE motif and caffeoyl or galloyl group of inhibitors play a critical role in the inhibition of integrase activity, and the binding affinity between integrase and inhibitors was improved when the side chain groups were galloyls. The linear interaction energy (LIE) method was used to calculate the binding free energies of HIV-1 integrase and their inhibitors, the predicted values are in good agreement with the experimental data, with a root-mean-square deviation (RMSD) of 1.39 kJ•mol-1. The above results provide useful information for structure-based HIV-1 integrase inhibitor design.

Key words: HIV-1 integrase inhibitor, Integrase, Molecular dynamics simulation, Dicaffeoyl group, Digalloyl group