For torsion-profile targets, relative energies were calculated with respect to the minimum energy on the grid for the reference QM torsion profile, as well as MM torsion profile. While evaluating the MM torsion profiles, to avoid large structural changes a harmonic positional restraint with a force constant of 1 kcal/mol/Å 2 , was applied on atoms not involved in the torsion. The energy contributions from the restraints were removed before comparing with the QM energies. The four atoms involved in the torsion were constrained during MM optimization. 10