Figure compares MBE(3) errors in across the data set, using three different paradigms to construct the binding-site model: eq. 6 with τ 2B = 2.5 × 10 -4 E h , a d = 6 Å model, and finally an Arpeggio model ob- tained using rinrus. For three of the four protein-ligand complexes, all of these models overestimate the interaction strength whereas for 1BOZ they all underestimate it, suggesting there may be an enzyme size-related bias that is common to all three algorithms. None of these three procedures consistently outperforms the others but the τ 2B approach stands out as the most reliable overall, with a mean absolute fragmentation error of 0.8 kcal/mol for MBE(3) calculations using HF-3c. Furthermore, the τ 2B = 2.5 × 10 -4 E h method also affords the smallest fragmentation error for MBE (2), which is 1.7 kcal/mol when averaged over the four complexes. However, the 6 Å model is only slightly less accurate on average, and more accurate in two out of four complexes. It is also considerably less expensive.