The Study Of Interaction Mechanism Of Chitinase With Inhibitors Based On Molecular Dynamics Simulations

Chitinase is widely distributed in nature, including most microorganisms andplants and animals (viruses, bacteria, fungi, insects, and some plants). And some ofChitinase plays an important role in the process of some fungi and insects’ growth,development and reproduction. Chitinase inhibitor can take a specific binding withchitinase, and can inhibit the biological activity of chitinase. It has antimicrobial andinsecticidal effect because the inhibit can prevent the insects’ normal developmentand microorganisms’ value-added process. All of these effects, making the chitinaseinhibitor has the chance to become the widely applied in biological insecticides andfungicides in agriculture, food and medical fields.In this study, the binding of theenzyme chitinase A1(afChiA1) from the plant-type A. fumigatus with four potentinhibitors, allosamidin (ASM), acetazolamide (AZM),8-chloro-theophylline (CTP)and kinetin (KIT) is investigated by molecular docking, molecular dynamics (MD)simulation, and binding free energy calculation.In this paper, these four inhibitor-chitinase binding complex were studied bymolecular dynamics simulation. By using molecular docking method to determine thestructure of inhibitor-chitinase complex structure. The binding energies changes ofinhibitor-chitinase can be got by using molecular dynamics simulation. Preliminarysure the binding activity site of chitinase inhibitor-protein. According to the freeenergy calculation and energy decomposition analysis, it can get the changes ofbinding free energy between the amino acid residues and the inhibitor. Finalized thekey amino acid which is in the chitinase activity center.The research results reveal that the electrostatic interactions play an importantrole in the stabilization of the binding of afChiA1with inhibitors. Based on the binding energy of afChiA1-ligands, the key residues (Gln37and Trp312) in the activebinding pocket of the complex systems are confirmed by molecularmechanics/Poisson-Boltzmann surface area method, and the active inhibitors, ASMand AZM, both could form strong interaction with Gln37and Trp312, and thenon-active ligands, CTP and KIT, could not interact with these two residues, which isconsistent with the result of experimental report. Then, it is identified that Gln37andTrp312should be one of the important active site residues of afChiA1.