Removing all restraints (Sage+BespokeFit (no restraints)) slightly improves the fit to the QM potential energy surface (0.35 kcal/mol), as might be expected. However, this is at the expense of increasing the distances between QM and MM optimized structures (maximum RMSD between optimized structures increases to 0.75 Å). An alternative scheme that we have implemented allows us to add the RMSD between QM and MM optimized structures directly into the ForceBalance objective function (Supporting Information Section S1.2). This removes the need for weak restraints and adds small improvements in both energetic (RMSE reduced to 0.35 kcal/mol) and geometric (RMSD reduced to 0.57 Å) measures of agreement with QM. For consistency with the base FF, however, we retain the Sage+BespokeFit method, with weak restraints, as the default behavior in BespokeFit.