Molecular Simulation Of The Interaction Between Imidazole Glycerol Phosphate Dehydrase And Nitrogen-Containing Heterocyclic Phosphate Inhibitors

A series of nitrogen-containing heterocyclic compounds as imidazole glycerol phosphate dehydrase (IGPD) inhibitors were successfully screened based on IGPD substrates; however, the mechanism is not clear. In this study, the B3LYP density functional theory method with the 6-31G** basis set as implemented in the Gaussian 03 program was selected to optimize the nitrogen-containing heterocyclic phosphates. These complex structures were constructed using molecular docking and optimization. The mode of interaction was discussed with regards to their electronic structures (frontier orbital energies and composition, the atomic charges, the natural bond orbital, etc.) and complex spatial structures (recognition functional domains of the inhibitor of IGPD, intermolecular hydrogen bonding, van der Waals interactions, etc.). The charge distribution of the nitrogen-containing heterocycle, the phosphate ion charge distribution, and the frontier orbital LUMO energy levels of the inhibitor were determined to be intrinsic factors that affect inhibitor activity. The conclusion of our study will provide valuable information for the screening and optimization of new herbicides targeted at IGPD.