Automated Docking of NADH to the Active Site of Nitric Oxide Reductase from Fusarium Oxysporum and Semi-empirical Calculations of the Electron Transfer Mechanism and the Hydrogen-bonding Network

摘要

The electron direct transfer from NADH to the active site of nitric oxide (NO) reductase (NOR) from Fusarium Oxysporum and the hydrogen-bonding network in the NOR heme pocket were investigated using docking simulations and quantum chemistry calculations. The products and substrates were docked into the active site of NOR using the genetic AutoDock algorithm. According to the lowest-energy NOR-NADH conformers obtained, the nicotinamide radical of NADH localized near the NO ligand molecule in the active site via the 2 water molecules Wat74 and Wat292.To investigate the quantum chemistry interactions, we carved out the active site model from the lowest-energy complex structure obtained. Based on the enzymatic environment of NOR, the model was composed of the amino-acid residues that constitute the positive-charge cluster and the water molecules that are part of the hydrogen-bonding network. Applying the SAM1 single-point SCF calculation to the active site model, we detected a quantum chemistry interaction between NADH, the NO ligand, and the 2 water molecules nearest the NO ligand.