关键词: 锌络合物, 酶抑制剂, 白明胶酶, MMP-2, 分子对接, 金属蛋白酶, 分子动力学

The binding mode of MMP-2 with hydroxamate inhibitors was studied by using molecular dynamics (MD) simulations. In MD simulations, a bonded model for the catalytic zinc center was used to represent the bonded interactions between zinc center and enzyme/inhibitor. From the simulated results, it can be seen that the substituent on R^1 site will form good steric complementarity with the S1 hydrophobic pocket of MMP-2; consequently, produce strong van der Waals contacts and hydrophobic interactions. Moreover, the hydrogen bonds between receptor and ligand was critical for ligand binding,and two inhibitor can form 5 and 8 hydrogen bonds with MMP-2, respectively. The stronger binding affinity of B than A may be derived from the more favorble hydrogen-bonding interactions. In MD simulations, the coordination of the inhibitor's hydroxamate group to the catalytic zinc atom was maintained very well for the entire simulation time. The predicted complex structure of MMP-2 with hydroxamates will be very important for us to take into insight the potetial mechanisms of the intermolecular interactions between inhibitor and receptor, especially with respect to the design of new compouds.

Key words: ZINC COMPLEX, ENZYME INHIBITOR, MOLECULAR DYNAMICS