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羟基异吲哚酮类衍生物与HIV-1整合酶的分子模拟研究

杜文义, 胡建平, 左柯, 刘嵬, 梁立, 代田洋

杜文义, 胡建平, 左柯, 刘嵬, 梁立, 代田洋. 羟基异吲哚酮类衍生物与HIV-1整合酶的分子模拟研究[J]. 中国药科大学学报, 2016, 47(5): 551-559. DOI: 10.11665/j.issn.1000-5048.20160508
引用本文: 杜文义, 胡建平, 左柯, 刘嵬, 梁立, 代田洋. 羟基异吲哚酮类衍生物与HIV-1整合酶的分子模拟研究[J]. 中国药科大学学报, 2016, 47(5): 551-559. DOI: 10.11665/j.issn.1000-5048.20160508
shu
DU Wenyi, HU Jianping, ZUO Ke, LIU Wei, LIANG Li, DAI Tianyang. Molecular simulation study on the recognition between hydroxy isoindolin ketone derivatives and HIV-1 integrase[J]. Journal of China Pharmaceutical University, 2016, 47(5): 551-559. DOI: 10.11665/j.issn.1000-5048.20160508
Citation: DU Wenyi, HU Jianping, ZUO Ke, LIU Wei, LIANG Li, DAI Tianyang. Molecular simulation study on the recognition between hydroxy isoindolin ketone derivatives and HIV-1 integrase[J]. Journal of China Pharmaceutical University, 2016, 47(5): 551-559. DOI: 10.11665/j.issn.1000-5048.20160508
shu

羟基异吲哚酮类衍生物与HIV-1整合酶的分子模拟研究

  • 1.

    成都大学，四川抗菌素工业研究所，药食同源植物资源开发四川省高校重点实验室

  • 2.

    乐山师范学院化学学院

基金项目: 国家自然科学基金资助项目(No.11247018,No.11147175)；四川省教育厅科研重点项目资助项目(No.12ZA066)；乐山市科技计划资助项目(No.14SZD018)

Molecular simulation study on the recognition between hydroxy isoindolin ketone derivatives and HIV-1 integrase

摘要

    摘要
  • 摘要: 为了研究羟基异吲哚酮类衍生物与HIV-1整合酶识别的机制以及构象变化，采用AutoDock对58个羟基异吲哚酮类衍生物与整合酶进行了分子对接，并对抑制HIV-1整合酶活性较好的两个化合物所形成的复合物模型分别进行了16 ns的分子动力学模拟。基于对接复合物模型分析给出了化合物与整合酶结合的主要作用力，通过分析氢键以及构象的变化，发现氨基酸残基N155与D64之间的氢键是维持整合酶催化活性所必需的DDE基序结构稳定的关键。另外，氨基酸残基Y143所在的loop区与羟基异吲哚酮类衍生物之间的疏水作用力在受体-配体识别的过程中具有重要的作用。
    Abstract: To discuss the conformational change and the recognition mechanism of hydroxy isoindol ketone derivatives with HIV-1 integrase, fifty-eight hydroxy isoindol ketone derivatives were docked to the integrase using AutoDock program. Molecular dynamics simulation with 16 ns was carried out for the two complex modes, respectively, in which the corresponding small molecules exhibited strong inhibition ability. Main force acting on the association of small molecules with integrase was explored based on the docking complex model. After analyzing the hydrogen-bond and conformational changes, it was found that the hydrogen-bond between N155 and D64 was the key factor maintaining the DDE motif stability. Furthermore, the hydrophobic interactions between the loop region where Y143 located and the hydroxy isoindol ketone derivatives were found to play an important role for their recognition.
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  • 刊出日期:  2016-10-24

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