In Fig. , we compare the VDD charges of SAM, CAT, and the catalytically-active Mg 2+ cation as well as the QM/MM reaction energy obtained for the atom-economical QM regions constructed using CSA, FSA, and PCVA to those obtained for PCVA-constructed QM regions of increasing size discussed in Section 6. Note that the size of the atom-economical QM regions of 16 amino acids is in between those of QM regions 4' (13 amino acids) and 5'