For all RMSD calculations, the initial input coordinates for T4 lysozyme with p-xylene were used as the reference state; all simulations started from this state. The global backbone RMSD was computed using all backbone atoms in the system. The local backbone RMSD was computed using backbone atoms from all residues within 5Å of the Val111 sidechain and the Val111 backbone RMSD was computed using the Val111 backbone atoms.