Preparing receptor structures. We prepared the receptors for docking by a three-step process. For consistency with our generated ensembles, we first read the crystal structure into Rosetta and removed any crystallographic buffer or water molecules, but retained metal ions of the following types: Na, Fe, Mg, K, Mn, Zn, and Ca. Using Rosetta, we filled in missing atoms for incomplete protein residues. We then define a bounding box surrounding each initial ligand used as the search space for subsequent docking. For this study, we accepted the protonation states of titratable residues found in PDBbind.