| 基于“底物包膜”假说筛选新型HIV-1蛋白酶抑制剂 |
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| 引用本文： | 缪有盼,李爱秀,刘涛,吴可柱,马翼. 基于“底物包膜”假说筛选新型HIV-1蛋白酶抑制剂[J]. 化学学报, 2009, 67(10): 1098-1102 |
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| 作者姓名： | 缪有盼 李爱秀 刘涛 吴可柱 马翼 |
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| 作者单位： | (a中国人民武装警察部队医学院基础医学部药物设计实验室 天津 300162) (b中国人民武装警察部队医学院职业与环境危害生物标志物天津市重点实验室 天津 300162) (c南开大学元素有机化学国家重点实验室 天津 300071) |
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| 基金项目： | 国家自然科学基金，天津市科技攻关计划重点科技攻关专项基金 |
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| 摘 要： | 基于“底物包膜”假说, 以现有HIV-1蛋白酶抑制剂Darunavir为模板构建药效团模型并对中药化学数据库进行搜索; 采用分子对接方法进一步考察化合物与HIV-1蛋白酶结合情况及其与“底物包膜”符合程度, 优先选出两个化合物Annomonicin和去乙酰蟾蜍它灵; 应用分子动力学方法对这两个化合物进行动力学模拟, 观察它们与蛋白酶结合的复合物在动力学过程中的稳定性并计算其结合自由能, 综合评价筛选结果, 最终确定化合物Annomonicin具有更潜在的深入研究价值.
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| 关 键 词： | “底物包膜”假说 药效团 分子对接 分子动力学模拟 HIV-1蛋白酶抑制剂 |
| 收稿时间： | 2008-11-14 |
| 修稿时间： | 2008-12-31 |
Screening Novel HIV-1 Protease Inhibitors Based on the Substrate Envelope Hypothesis |
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| Miao Youpan,Li Aixiu,Liu Tao,Wu Kezhu,Ma Yi. Screening Novel HIV-1 Protease Inhibitors Based on the Substrate Envelope Hypothesis[J]. Acta Chimica Sinica, 2009, 67(10): 1098-1102 |
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| Authors: | Miao Youpan Li Aixiu Liu Tao Wu Kezhu Ma Yi |
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| Affiliation: | (a Drug Design Laboratory of the Basic Science Department, Medical College of Chinese People’s Armed Police Force, Tianjin 300162, China) (b Tianjin Key Laboratory for Biomarkers of Occupational and Environmental Hazard, Medical College of Chinese People’s Armed Police Force, Tianjin 300162, China) (c State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin 300071, China) |
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| Abstract: | Based on the Substrate Envelope Hypothesis and the available HIV-1 protease inhibitor darunavir, a new pharmacophore model of HIV-1 protease inhibitors was constructed, and applied to the Traditional Chinese Medicine Database searching. By molecular docking, two compounds of novel structure that not only bind well with the HIV-1 protease, but also fit well within the substrate envelope, were found. They were annomonicin and desacetylbufotalin. Then molecular dynamics simulations were used to study these two... |
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| Keywords: | substrate envelope hypothesis pharmacophore molecular docking molecular dynamics simu- lation HIV-1 protease inhibitor |
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