Chem. J. Chinese Universities ›› 2009, Vol. 30 ›› Issue (8): 1592.

• Articles • Previous Articles     Next Articles

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.

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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