高等学校化学学报 ›› 2009, Vol. 30 ›› Issue (8): 1592.

• 研究论文 • 上一篇    下一篇

基质金属蛋白酶的新型抑制剂效能的理论研究

李岱霖1, 郑清川1, 张红星1, 姬海涛2, 杨金刚2, 房学迅2   

  1. 1. 吉林大学理论化学研究所, 理论化学计算国家重点实验室,
    2. 分子酶学工程教育部重点实验室, 长春 130023
  • 收稿日期:2008-03-24 出版日期:2009-08-10 发布日期:2009-08-10
  • 通讯作者: 张红星, 男, 博士, 教授, 博士生导师, 主要从事量子化学计算研究. E-mail: zhanghx@jlu.edu.cn
  • 基金资助:

    国家自然科学基金(批准号: 20573042)、国家科技支撑计划重点项目(批准号: 2006BAE03B01)、高等学校博士学科点专项基金(批准号: 20070183046)和吉林大学基本科研业务费项目(批准号: 200810018)资助.

Theoretical Studies on the Potency of Novel Matrix Metalloproteinases Inhibitors

LI Dai-Lin1, ZHENG Qing-Chuan1, ZHANG Hong-Xing1*, JI Hai-Tao2, YANG Jin-Gang2, FANG Xue-Xun2   

  1. 1. State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry,
    2. Key Laboratory for Molecular Enzymology and Enzyme Engineering of Ministry of Education, Jilin University, Changchun 130023, China
  • Received:2008-03-24 Online:2009-08-10 Published:2009-08-10
  • Contact: ZHANG Hong-Xing
  • Supported by:

    国家自然科学基金(批准号: 20573042)、国家科技支撑计划重点项目(批准号: 2006BAE03B01)、高等学校博士学科点专项基金(批准号: 20070183046)和吉林大学基本科研业务费项目(批准号: 200810018)资助.

摘要:

采用分子力学和分子动力学方法, 考察了MMPs抑制剂、焦性没食子酸(Pyrogallic acid)和杨梅黄酮(Myricetin)与MMP-7的具体结合方式以及相互作用的情况. 研究结果表明, 在与MMP-7结合时, 杨梅黄酮比焦性没食子酸具有更高的亲合性, 因此杨梅黄酮对MMP-7有更好的效能, 这与实验测得的活性顺序相符. 另外, 密度泛函理论的计算结果表明, 此类抑制剂能够通过ZBG以单配位的形式与MMPs的Zn2+相互作用. 理论计算的结果可能有助于抑制剂的设计及其效能的改善.

关键词: 基质金属蛋白酶; 分子对接; 密度泛函理论; 焦性没食子酸; 杨梅黄酮

Abstract:

By means of molecular mechanics and molecular dynamics methods, the binding modes and inte-ractions between newly found matrix melalloproteinases(MMPs) inhibitors, Pyrogallic acid and Myricetin, and MMP-7 were investigated in the present study. The calculated results show that the binding affinity between Myricetin and MMP-7 is higher than that between Pyrogallic acid and MMP-7 when they bind to MMP-7, thus Myricetin is more potent on MMP-7 than Pyrogallic acid. This is in agreement with the inhibitory activity order from experiments. Furthermore, the density functional theory calculation results indicate that the inhibitors can bind to the zinc ion of MMPs with ZBG in a monodentate way. The theoretical results may be helpful for the structure-based design of inhibitors with improved potency.

Key words: Matrix melalloproteinases; Molecular docking; Density functional thoery; Pyrogallic acid; Myricetin

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