To compare the performance, refinement runs were carried out with each type of restraints. In addition to the refinement with restraints, simulations without restraints were conducted to revisit and reaffirm the benefit of using restraints with current simulation protocols. Sampling in each refinement run involved five trajectories of MD simulations, each performed for 100 ns. Sampled protein conformations were recorded for every 50 ps. Consequently, 10,000 structures were generated during each refinement run.