Even without the supersystem correction, results in Fig. indicate that a two-body expansion can achieve ∼ 1 kcal/mol accuracy for E a using various density functionals. Low-cost supersystem corrections reduce this to ∼ 0.5 kcal/mol. MBE( ) is an order-of-magnitude more accurate than MBE(2) and achieves ∼ 0.1 kcal/mol accu- for a single-point calculation on the COMT enzyme-substrate complex, at the ωB97X-D/def2-SVP level. The supersystem calculation contains 6,042 basis functions and was performed on a single 28-core node (Dell Intel Xeon E5-2680 v4). Fragment calculations were performed on the same hardware with 7 worker processes per node, each using 4 cores.