were selected as references for the umbrella replicas. The difference between the dihedral angle in the selected frames and the target angle was always below 0.1 • . Then, we performed 36 umbrella sampling simulations of 11 ns with a harmonic restraining potential centered at the reference dihedral angle and a force constant of 418.4 kJ mol -1 rad -2 . We used the WHAM procedure, implemented in GROMACS, to unbias these umbrellas and obtain free energy profiles associated with the full rotation of the dihedral angle.