The reference ensembles were extracted from MD simulations performed using the enhanced sampling method REST2 , following the set-up described by Waibl et al. . GROMACS 2023 with the PLUMED [71-73] 2.9.1 plugin was used. Simulations were performed for 100 ns and 200 ns for set C and P, respectively. Eight replicas and a quadratic scheme to distribute the scaling factors between 1 and 0.125 were applied.