基质金属蛋白酶的新型抑制剂效能的理论研究

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.

Theoretical Studies on the Potency of Novel Matrix Metalloproteinases Inhibitors

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.