Virtual screening for the discovery of novel urease inhibitors of rumen bacterial urease
Zhao, S.; Togtokhbayar, N.; Narantuya, B.
Show abstract
The inhibition of urea hydrolysis by rumen bacterial urease presents a promising strategy to enhance dietary nitrogen utilization efficiency in animal production while mitigating environmental nitrogen pollution. In this study, we employed comparative modeling using Modeller to determine the three-dimensional structure of urease from the ruminal bacterium Ruminococcus albus 8 (RaUrease), based on the crystal structure of Helicobacter pylori urease (HpUrease, PDB ID 1E9Z). Through molecular dynamics simulation conducted for 20 ns using the AMBER force field within the Gromacs system, we generated a reliable RaUrease structure and subsequently evaluated the stereochemical quality of the protein model. Virtual screening identified 12 commercially available compounds as potential urease inhibitors, based on their binding energies (<-9.8 kcal mol-1). Characterization of the RaUrease-binding site for the compound exhibiting the highest predicted inhibitory activity revealed that van der Waals interactions play a more significant role than hydrogen bonding in rumen bacterial urease binding. These findings provide valuable insights for the design of novel urease inhibitors tailored for ruminants, offering potential solutions to reduce nitrogen pollution associated with livestock production.
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