Acta Chimica Sinica ›› 2009, Vol. 67 ›› Issue (19): 2177-2183. Previous Articles     Next Articles

Original Articles

HIV-1整合酶与芳香二酮酸类抑制剂相互作用的分子模拟研究

胡建平*,a  张小轶b 唐典勇a 常珊b   

  1. (a乐山师范学院化学与生命科学学院 乐山 614004) (b北京工业大学生命科学与生物工程学院 北京 100124)
  • 投稿日期:2009-02-16 修回日期:2009-04-16 发布日期:2009-06-15
  • 通讯作者: 胡建平 E-mail:hujianping@emails.bjut.edu.cn;lion_hjp@yahoo.com.cn
  • 基金资助:

    四川省自然科学基金;四川省教育厅项目

Study on the Interactions between HIV-1 Integrase and Aryl Diketoacid Inhibitors with Molecular Simulation Methods

Hu, Jianping*,a     Zhang, Xiaoyib     Tang, Dianyong    Chang, Shanb   

  1. (a College of Chemistry & Life Science, Leshan Teachers College, Leshan 614004) (b College of Life Science & Bioengineering, Beijing University of Technology, Beijing 100124)
  • Received:2009-02-16 Revised:2009-04-16 Published:2009-06-15

The recognitions and interactions of a series of aryl diketoacid (ADK) inhibitors with HIV-1 integrase (IN) were studied via molecular docking method. The results indicate that the inhibitors bind to the pocket (formed by Asp64~Leu68, Thr115~Phe121, Gln148~Lys159 and Mg2+ ion) of IN, and the inhibiting mechanism is similar to that of 5CITEP. Molecular dynamics simulation and MM/PBSA methods were used to calculate the binding free energy between ADK inhibitors and IN. The calculated binding free energy agrees well with experimental data, and the average absolute deviation is 3.6 kJ/mol. It was also found that the formation of the complex was mainly driven by the favorable van der Waals’(VDW) interactions in the system and the favorable non-polar item of the solvent effect. Correlation analysis shows that the binding free energy has obvious linear correlation with the hydrophobic interaction (R=0.61), from which a good model predicting the binding free energy of ADK inhibitors with HIV-1 IN has been obtained through a multiple linear regression method. All the above simulation results provide us with some helpful instruction for the anti-HIV drug design based on the structures of inhibitors.

Key words: aryl diketoacid, integrase, binding free energy, correlation, molecular design