| Zinc proteases are a class of proteolytic enzymes containing zinc, whose function generally depends on the enzymatic catalytic zinc domain, while it’s a divalent zinc ion state. They participate in a variety of metabolic activity in the biological material, and affect indirectly the physiological functionsin of tissues and bones in living body. And the disorder of zinc protease easily lead to a variety of diseases, such as cancer, hypertension and arthritis and so on. The biggest difference between metalloproteases and other proteases, such as serine protease, aspartic protease, is the one or two metal ions belong to the active region, which most of metalloproteases metal contains divalent zinc ions. Function of metal ions is to activate water molecule, so that attack the carbonyl of peptide bonds by nucleophilic attack.Using theoretical calculations to predict the interaction of macromolecules and the enzyme inhibitors are widely used in the design of zinc metalloproteinase inhibitor. Theoretical study of interaction between enzyme--inhibitor can reach the atomic level and even on the electronic leve. It can be enough to get directly in the macromolecular enzyme catalysis relevant information which is of great significance to the design of small molecule inhibitors.Studies have shown that the MMP family members has been found that not all the members can become cancer drugs target enzymes, only MMP-1, MMP-2 and MMP-7 can be used as an effective anti-cancer drugs target enzymes, while the overexpression of MMP-7 were found in colon cancer and other malignant cells. Therefore, the inhibition of MMP-7 is very necessary as a means of controlling the tumor cells metastasis. We designed three series of Nitro inhibitor compounds and molecular docking study of three series of compounds were used to research the influences of changing the side chain in the structure to gain selectivity.In addition, we also study the kinetics for small molecule 1a to 1d against MMP-1 and MMP-7 respectively, and for small molecule compounds 2a to 2d against MMP-7by dynamics test. Molecular docking and dynamics test results show that although Ki values obtained are very different but the inhibitory effect shows the same order of priority of small molecules. The reason of individual differences is likely to the setting during the whole docking. |
