Examining the MBE(n) results in Fig. , we observe that MBE(2) consistently underestimates |∆E int | in both basis sets, due to missing nonadditive polarization. MBE(3) calculations overestimate |∆E int |. In the def2-ma-SVP basis set where we are able to demonstrate convincing convergence with respect to system size, the two-body result is underbound by about 2 kcal/mol while the three-body result is overbound by about 1 kcal/mol, as compared to a conventional calculation at the same level of theory. For models larger than 700 atoms, convergence of the MBE(2) and MBE(3) approximations to ωB97X-V/def2-ma-SVP track the conventional result quite well, albeit with constant offsets. For small models, however, that offset is masked and both the MBE(2) and MBE(3) results are in fortuitously good agreement with conventional supramolecular calculations. Unless these studies are pushed to the N → ∞ limit, one might erroneously conclude that three-body effects are unimportant. Furthermore, a 200-atom model affords an interaction energy |∆E int | that is 10 kcal/mol smaller than the converged value! If the triple-ζ calculations are indeed converged at the 665-atom model, then the MBE(2) calculations are are underbound in that case by about 2 kcal/mol while MBE(3) calculations are overbound by perhaps 3 kcal/mol. Regardless of where the converged tripleζ result for ∆E int may lie, we can state that MBE(2) and MBE(3) estimates bracket the conventional value by about 3.5 kcal/mol at the double-ζ level versus ≈ 5.5 kcal/mol at the triple-ζ level. These are large ranges by the standards of benchmark accuracy in smallmolecule quantum chemistry calculations and it is not immediately clear whether this level of agreement is acceptable. That issue is taken up in Section 3 .1 .4, where we discuss the appropriate level of accuracy for largescale electronic structure calculations of protein-ligand interaction energies. Before that, however, we examine convergence of the radial enzyme models with respect to both model size (N ) and level of approximation (n), in Section 3 .1 .2. Basis-set convergence is examined in Section 3 .1 .3.