This approach was taken primarily for computational efficiency, but it carries the risk of creating mismatches between the MM and QM vibrational modes. To test for this possibility, we also carried out single-point comparisons of vibrational frequencies where the MM frequencies and normal modes are permuted to maximize overlap with the QM normal modes. The permutation was carried out by computing the massweighted overlap matrix between each pair of QM and MM normal modes followed by solving the linear sum assignment problem. The objective function was then computed using the resulting matched pairs of QM and MM frequencies. Quantum mechanical energy profiles were generated for dihedral angles in the Roche and Coverage sets.