The 1HSG:indinavir complex consists of a small ligand bound to HIV-2 protease and has become a model system for testing quantum-chemical methods for noncovalent interactions. This structure was taken from Ref. 105. For the other three complexes, crystal structures were obtained from the protein data bank, 108 which were then protonated using the H++ web server. The resulting structures were relaxed using the GFN2-xTB semi-empirical quantum chemistry method, 110 using a generalized Born model for water. Relaxed structures were trimmed, using a 5 Å cutoff (with respect to the ligand) for the 181L and 1LI2 complexes and a 2.5 Å cutoff in the case of 1O44 where the ligand is much larger. The coordinates that we used in the quantum chemistry calculations can be found in the Supporting Information.