In Fig. we reported the trans-to-cis free energy profiles in proline computed at the DFTB2-MIO (black solid line), DFTB2-OB2 (red solid line), and DFTB3-3OB (blue solid line) levels of theory. For the sake of comparison, we also reproduced the profiles computed at the MM level of theory, using a modified set of Amber99sb parameters reported in the literature, where the heights of the barrier associated with the peptidyl bond torsion were adjusted to match the experimental data (black dashed line), and at the B3LYP/6-31G* level of theory (green dashed line), which underestimates the height of the barrier, probably due to the self-interaction error. . To compare the profiles, the zero has been arbitrarily set to the free energy value of the trans isomer.