To assess the accuracy of atom-economical QM regions, we constructed regions with the 16 highest ranked amino acids based on the indicators of standard and cryst PCVA and compared the corresponding charges and reaction energies to the best estimates (see Fig. and). Regarding VDD charges, standard delivers a charge 0.15 higher than for the best estimate (-0.25). The cryst saaPCVA performs much better with a charge of -0.23. The CDA-constructed QM region results in a charge lying between the two PCVA variants at about -0.15. Concerning the reaction energy, we observed the reversed behavior for the two PCVA schemes. Here, standard performs better with a reaction energy about 10 kcal/mol below the best estimate (9 kcal/mol) while for cryst, the reaction energy is nearly 20 kcal/mol higher. The CDA result is again between the two with about 22 kcal/mol. Table compares the residue ranks of the two different PCVA variants and CDA with each other. What stands out is that the residues detected by CDA are mainly charged residues, which are often not detected by saaPCVA, such as ARG98, ARG99, GLU104 or LYS112. On the other hand, CDA misses several neutral residues very close to the ligand, which are detected by PCVA, e.g., GLY171, SER211 or LEU230. As these residues may also have an important catalytic role, CDA is considered to not perform reasonably in this case. In the comparison between standard and cryst PCVA there are only minor differences. The first approach ranks ASN213 and VAL231 unter the highest ranked 16 residues, while the latter one detects CYS126 and ALA163, exclusively. All other 14 residues are part of both constructed atom-economical QM regions.