With the exception of 1O48, it is possible to obtain sub-kcal/mol fidelity with respect to a full-protein calculation using only MBE(2), if the model is constructed using a sufficiently small value of the two-body energy threshold (τ 2B ) in eq. 6. Even for 1O48, sub-kcal/mol fidelity is achievable but in that case it requires MBE(3), and comes with a significant increase in cost. For 1O48, MBE(3) is consistently and significantly more accurate than MBE(2) but for the other three systems, MBE(2) and MBE(3) results are typically within ∼ 1 kcal/mol of one another.