Once the parameter optimization was complete, we analyzed the accuracy of the new parameters by computing deviations between QM and MM geometries and energy profiles. In particular, starting from the QM optimized geometry for each fragment at each point on the torsion scan, the conformer underwent a full MM relaxation, with only the targeted torsion angle being fixed. The MM energy was recorded at the final relaxed geometry and the root mean square error (RMSE) was computed over the full scan, relative to the QC reference relative energies. The root mean square deviation (RMSD) was also computed between QM and MM relaxed coordinates, and the maximum value across the scan was recorded.