In the above expression, the solvation free energy, ∆G sol solute , of a system is assessed by the microscopic (unscaled) PDLD method. The superscripts of the solvation energy, 'l+p' and 'l'+p', refer to ligand-protein complex in their charged states and the same complex with a non-polar ligand (i.e., all atomic charges of the ligand are assigned to zero). The parameter, not directly tied to the actual protein "dielectric constant", accounts for implicitly treated contributions. Typically, when protein reorganization energy is explicitly considered, it is reasonable to use. U qμ l reflects the vacuum interaction between ligand charges and protein dipoles. Finally, calculating the catalytic effect entails assessing the binding energy in both the ground and transition states by employing,