Crystal structures were obtained from the PDB and protonated using the H++ web server, specifying pH = 7.0, salinity of 0.15 M, ε in = 10, and ε out = 80. The large ligands were protonated separately using the PyMol program. As in previous work, the geometry was then relaxed using the GFN2-xTB semi-empirical method, in conjunction with a generalized Born/solvent-accessible surface area (GBSA/SASA) implicit solvation model for water. Most crystallographic water molecules were removed after relaxation, although those coordinated with the Cl -ions were retained, as were any crystallographic water molecules within 2.5 Å of the ligand.