Study Of Molecular Dynamic Simulation Of The Nitro Dipeptide Compounds As The Inhibitors Against Thermolysin

As a typical representative of zinc metalloprotease, to study the inhibitor of Thermolysin (TLN) can provide material for the study of the inhibitors of other classic zinc metalloproteinase. Generally, the ability of zinc-binding group (ZBG) to coordinate the zinc ion is to determine the main factors of the activity of the inhibitor of zinc metalloproteinase; On the other hand, the structure of the side chain of inhibitors have a wide selection, adjustment, optimization possible, which provides the possibility to achieve selective inhibition of zinc metalloproteinase. Therefore, on the basis of the selected ZBG, predict the impact of side chain structure of inhibition on theory, simplify subsequent experimental procedure, and to designed compound to meet the requirements, is an extremely important issue.Predicted the binding free energy between the enzyme and inhibitor, often using FEP, LIE and Molecular Mechanics-Generalized Born/Poisson Boltznann Surface Area (MM-GB/PBSA). Which, MM/GBSA method is relatively less time-consuming drive, and the accuracy of the binding free energy to meet the general requirements.By means of molecular docking, molecular dynamics and MM/GBSA methods, side chain optimization of the nitro dipeptide inhibitor for thermolysin inhibition performance impact were investigated in the present study. The calculated results show that when the side groups is isobutyl, it can improve the binding affinity for binding to TLN. Inhibitory constants and binding free energies of theoretical calculations is in agreement with the inhibitory activity order from experiments. These results may be a useful basis for the structure-based design of inhibitor of TLN.