Molecular Docking and Molecular Dynamics Simulations of Inhibitors Binding to Jack Bean Urease

From the bioassay tests, compound 2-acetyl-gamma-hydroxybutyric (COM) showed good inhibitory activity against Jack bean urease with IC50=375 mu mol.L-1. Then the molecular docking and molecular dynamics (MD) simulations were performed to investigate the interactions between Jack bean urease and inhibitor aceto hydroxamic acid (AHA) and COM. GOLD3.0 program was used to perform the docking, and Amber was used to model the docking complex structures of inhibitor-Jack bean urease. Nonbonded model used for the nickel ions provided good reproduction of the active site of Jack bean urease during the MD simulations. The results confirmed that both nickel ions were pentacoordinated in AHA-Jack bean urease model. The binding model of the COM-Jack bean urease showed that Ni(1) was pentacoordinated while Ni(2) was hexacoordinated. The models provided useful information for understanding of the interactions between inhibitors and the protein.