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化学学报
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化学学报 ›› 2010, Vol. 68 ›› Issue (20): 2029-2034.    下一篇

研究论文

HIV-1蛋白酶与抑制剂作用的结合自由能计算

伊长虹1,2，张庆刚*,1   

  1. (1山东师范大学物理与电子科学学院 济南 250014)
    (2山东交通学院数理系 济南 250023)
  • 投稿日期:2010-03-15 修回日期:2010-05-20 发布日期:2010-07-09
  • 通讯作者: 伊长虹 E-mail:yich_china@163.com
  • 基金资助:

    蛋白质与其抑制剂作用机制的分子动力学模拟和量子力学分析

Study of the Binding Free Energies between HIV-1 Protease and Its Inhibitors

Yi Changhong1,2 Zhang Qinggang*,1   

  1. (1 College of Physics and Electronics, Shandong Normal University, Jinan 250014)
    (2 Department of Mathematics and Physics, Shandong Jiaotong University, Jinan 250023)
  • Received:2010-03-15 Revised:2010-05-20 Published:2010-07-09

PDF

1890

被引次数

11

HIV-1蛋白酶是治疗艾滋病的重要靶标酶之一. 采用分子动力学模拟, 运用MM-PBSA方法计算了HIV-1蛋白酶与三个抑制剂BE4, BE5和BE6的结合自由能, 结果表明抑制剂P1/ 位置的苄基上双氟原子的不同位置对结合自由能产生不同的影响. 通过能量分解的方法考察了HIV-1蛋白酶的主要残基与三个抑制剂间的相互作用与识别, 结果表明三个抑制剂以相同的作用模式与HIV-1蛋白酶结合, 计算结果与实验结果基本吻合.

关键词: HIV-1蛋白酶, 分子动力学, MM-PBSA/GBSA, 结合自由能, 抑制剂

HIV-1 protease is an important target of AIDS chemotherapy. Molecular dynamics simulations followed by MM-PBSA analyses were performed to study the binding of inhibitors BE4, BE5 and BE6 to HIV-1 protease. The results show that positioning of the fluorine atoms on the benzyloxy group of P1/ of the inhibitors affects their binding free energies. Inhibitor-residue interactions calculated provide some insights into the mechanisms of enzyme-inhibitor binding. Our results indicate that the three inhibitors bind to HIV-1 protease in a very similar mode. The calculated data agree well with experimental findings.

Key words: HIV-1 protease, MM-PBSA/GBSA, molecular dynamics, binding free energy, inhibitor