QM/MM hybrid simulation of enzyme-Mn synergistic catalysis for quinazolinones: computational determination of activation energy and transition state

from experimental measurements and the overall computational error remained below 2.5%. In addition, optimization of Mn charge states substantially improved catalyst cyclability, with an approximately sevenfold enhancement in reuse performance. These findings demonstrate that the synergistic effect between Mn-mediated substrate pre-activation and the enzymatic hydrogen-bond network is the key factor underlying efficient quinazolinone formation, and they provide a reliable theoretical basis for the design of noble-metal-free hybrid catalytic systems for sustainable synthesis.