The initial equilibration of each simulated system involved the following steps: A given initial protein model was rotated to align its principal component axes to X, Y, and Z-axes and centered at a periodic rectangular simulation box with a marginal distance from the protein to the box edges of 9 Å. This protocol minimized overall system sizes to reduce computational costs. Explicit waters filled up the rest of the simulation box. Some of the water molecules were replaced randomly with either sodium or chloride ions as needed to neutralize the total charge of each system. Solvated systems were then locally minimized by the l-BFGS-b algorithm for up to 500 steps. Initial Langevin dynamics simulations were started from the minimized system for 1 ns in total with a 2-fs time step and a 0.01/ps friction coefficient. During these equilibration simulations, the temperature was first gradually heated up to the temperature used in the production simulations using the NVT ensemble. Then, equilibration was continued in the NpT ensemble at 1 bar with a Monte Carlo barostat to allow the box sizes to adjust. Throughout the equilibration, harmonic restraints were applied to Cα atoms with respect to their initial positions with a force constant of 0.5 kcal/mol/Å 2 . From the equilibrated structures, production simulations were carried out by using Langevin dynamics simulations with a 0.01/ps friction coefficient in the NVT ensemble. We used either a 4-fs time step with hydrogen mass repartitioning or a 2-fs time step with standard atomic masses (to reproduce our earlier CASP12 protocol).