The analysis of energy barriers calculated for both models by using B-QM and corrected with D3 dispersion and thermal energy corrections (Table ; see Table -S7 for all energies) indicates that the proR-TS ES is energetically more favorable (40.4 kJ/mol) and hence more probable compared to the proS-TS ES (62.2 kJ/mol). However, the difference is not large enough to exclude a reaction via proS-TS ES , rendering both processes kinetically possible. The energy state of intermediate I1 is very similar in both models and turned out to be 32-34 kJ/mol lower (more stable) than that of the substrate-bound E:S state.