In the creation of QM models, we insist on automated methods that provide a reproducible, black-box approach to constructing structural models for QM calculations, without the use of any system-specific information beyond what is contained in a crystal structure. Structural models of the aforementioned protein-ligand complexes, containing anywhere from 120 to 1,726 atoms, were generated by one of several different approaches that are described in Section 2 .3.