Restraints were selected to optimally mimic native protein-ligand interactions by postprocessing a 6 ns simulation of the fully interacting complex. From the first frame, all heavy atoms in the protein within 10 Å of the ligand, and all heavy atoms in the ligand were selected. To avoid anchor points with poor correlation in position, the distances between all possible protein-ligand atom pairs from this selection were tracked over the trajectory, and the 200 pairs with the lowest standard deviation were selected. For multiple distance restraints, only the lowest variance pair for any anchor point was retained, provided that neither of the anchor points had already been selected for use in another restraint. For