*2.3. Molecular Docking*

Molecular docking studies were conducted to rationalize the binding mode of the pyrimidine derivatives using the MOE package [Molecular Operating Environment, 2016.0810; Chemical Computing Group ULC, 1010 Sherbrooke St. West, Suite #910, Montreal, QC, Canada, H3A 2R7, 2017]. The three-dimensional structure of the urease protein was retrieved from the Protein Data Bank (PDB ID 4GY7) [48]. Water molecules were removed, and the protonation step was performed. Energy minimization using default parameters was performed to achieve a stable conformation. The optimized geometries of the pyrimidine derivatives were docked to the active site of the urease protein. For docking studies, an induced fit protocol with the triangular matcher placement method and London dG scoring function were used. The interactive docking procedure was performed for all the optimized conformers of each compound in the active site. A score was assigned to each docked compound based on its fitting in the binding cavity and its binding mode (docking study protocol are provided in the Supplementary materials).

### **3. Results and Discussion**
