The MD simulations were performed with the multiple-GPU version of PMEMD (pmemd.cuda.MPI ) . The systems were NVT heated to 300K and NPT equilibrated for 5 ns, and the resulting equilibrated coordinates were used as the initial coordinates for the production simulations. The simulations were performed using periodic boundary conditions, with a nonbonded cutoff of 9 Å. The SHAKE algorithm was used to constrain the lengths of bonds involving hydrogen atoms. Pressure and temperature were regulated by a Monte Carlo barostat and a Langevin thermostat, respectively. Hydrogen mass repartitioning was enabled, to allow use of a long (4 fs) timestep . A prior study showed that this approach does not lead to significant differences in computed binding enthalpies . The simulations were run in 200 ns blocks, with each block seeded by a new random number. Coordinates and energies were recorded every 500 steps (2 ps).