Insight into the key active sites of afChiA1 based on molecular dynamics simulations and free energy calculations

Abstract

In this study, the binding of the enzyme chitinase A1 (afChiA1) from the plant-type Aspergillus fumigatus with four potent inhibitors, allosamidin (ASM), acetazolamide (AZM), 8-chloro-theophylline (CTP) and kinetin (KIT) is investigated by molecular docking, molecular dynamics simulation and binding free energy calculation. The results reveal that the electrostatic interactions play an important role in the stabilisation of the binding of afChiA1 with inhibitors. Based on the binding energy of afChiA1-ligands, the key residues (Gln37 and Trp312) in the active binding pocket of the complex systems are confirmed by molecular mechanics/Poisson–Boltzmann surface area method, and the active inhibitors, ASM and AZM, both could form strong interaction with Gln37 and Trp312, and the non-active ligands, CTP and KIT, could not interact with these two residues, which is consistent with the result of experimental report. Then, it is identified that Gln37 and Trp312 should be one of the important active site residues of afChiA1.