When we naively apply MBE(n) to a large COMT model with charged residues, however, we find that convergence is erratic. This is shown for the barrier height (activation energy E a ) in Fig. , where MBE(2) overestimates the barrier by 5.4 kcal/mol but MBE(3) underestimates it by 16.7 kcal/mol. To verify that charged residues are the problem, we prepared a second model of COMT in which fragments are combined to neutralize charge, e.g., a negatively-charged aspartic acid residue is combined with a positively-charged ligand, forming a single fragment. This increases the largest fragment size from 58 to 124 atoms but does not change any protonation states. Using this "charge-coordinated" model of COMT, we observe rapid convergence of MBE(n), such that two-and three-body calculations afford essentially identical values of both E a (Fig. ) and ∆ rxn E (Fig. ). Even one-body calculations perform reasonably well for the charge-coordinated model, due to the larger fragment size, but enlarging the fragments is not an attractive strategy for levels of theory beyond DFT.