For the alanine dipeptide, the 2-dimensional free energy surface corresponding to its Ramachandran angles was obtained. Windows were separated by 5 degrees. The starting structures for each window were obtained starting from a previously equilibrated structure by performing a short MD simulation with a force constant of 50 kcal/(mol rad 2 ). Sampling on each window used a 125 kcal/(mol rad 2 ) force bias. Simulations were performed both at the MM and ML/MM levels using 5 and 50 ps long NVT simulations, respectively. No QM/MM simulations were performed in this case due to the significant amount of QM simulations needed in order to obtain the free energy surface.