The MD package NAMD2.12 was used throughout the equilibration and production runs of all simulations. For each replica in an ensemble, energy minimizations were first performed with heavy protein atoms restrained at their initial positions. The initial velocities were then generated independently from a Maxwell-Boltzmann distribution at 50 K, and the systems were heated up to and kept at 300K within 60 ps. A series of equilibration runs, totalling 2 ns, were conducted, while the restraints on heavy atoms were gradually reduced. Finally, 4 ns production simulations were run for each replica for all ESMACS and TIES simulations.