The atomic charges of the QM region were determined from Electrostatic Potential (ESP) 45 charges, computed by Gaussian16 at the M06-2X/Def2-TZVP level with the inclusion of the SMD solvation model. These resultant charges were utilized to generate the restrained electrostatic potential (RESP)-fitted charges via AmberTools. The RESP charges were exclusively applied to the substrate and the reacting residues, Serine and Histidine, whereas the ENZYMIX force field was utilized for the atoms of the enzyme and water. All the calculations were carried out using the MOLARIS-XG package.