These two QM regions are again compared to the best estimate with respect to VDD ligand charges and the QM/MM reaction energy (see Fig. ). Regarding VDD charges, b-half and b-norm perform similar to PCVA for Mg 2+ and CAT. In contrast to PCVA, both b-half and b-norm are able to predict a positive ligand charge for SAM, where b-norm still overestimates the charge while bhalf underestimates it. Nevertheless, for b-half the SAM charge of about 0.1 is closer to the best estimate than for all PCVA or centrality-based approaches considered so far. Concerning the reaction energy, b-norm, delivers an energy of about -20 kcal/mol which is close to the PCVA but about 10 kcal/mol below the best estimate. Here, the b-half approach outperforms all other methods with -9.5 kcal/mol, nearly perfectly reproducing the best estimate.