Validation of Selected Parameters. In general, the performance of the best few parameter sets can be quickly assessed through simple tests such as PES scans, geometric analyses of stationary states, or comparison of predicted properties with available experimental data. However, in this work, to rigorously demonstrate the effectiveness of our parametrization approach, we conducted a more comprehensive validation through QM/MM MD simulations using the ASM. We combined energetic analyses on the best parameter sets with PCA performed on the collected MD trajectory frames (see PCA analysis description in the SI). This allowed us to evaluate both the energetic and structural accuracy of our parametrization by comparing results with limited HL QM/MM sampling along the reaction paths.