Steered molecular dynamics simulations were performed using pmemd.cuda from AM-BER22 40 with PLUMED v2.6.1, using BioSimSpace for input file preparation. Tutorials to implement steered MD simulations with BioSimSpace are available elsewhere. Simulations were run at a temperature of 300 K and 1 atm pressure, using Langevin dynamics with γ=2 ps -1 . Steering was carried out in both directions in two steps, i.e. inactive-intermediate- .