The need for additional screening is dramatically underscored by MBE(4) results for 1BOZ, the largest enzyme considered here. For this system, the difference between a 8 Å cutoff and a 12 Å cutoff increases the number of tetramers from 82,975 to 758,495 and increases the error from 0.5 to 20.1 kcal/mol. The MBE(4) entry in Table 3 represents the larger cutoff radius, which two-body calculations suggest is required to reach convergence, but using that cutoff results in a MBE(4) estimate of ∆E int that is substantially less accurate than the MBE(3) estimate. Meanwhile, MBE(4) results with an 8 Å cutoff afford ∆E int = -31.8 kcal/mol for 1BOZ, which within 0.5 kcal/mol of the supersystem result.