with consistent application of MBE(n) to compute both the energy of the isolated protein (E P ) and that of the protein-ligand complex (E P:L ). The ligand energy (E L ) is computed without fragmentation. Many of the n-body terms will cancel in eq. 5 and need not be computed. The present version of Fragme∩t identifies these terms a priori and removes them, using the algorithm described in Ref. 22, which leads to considerable cost savings for ∆E int calculations. However, the present calculations were performed contemporaneously with that development and this savings was not exploited. As such, timing data reported here reflect the cost of all n-body terms in eq. 5, subject only to the distance cutoff R cut . Use of eq. 5 is subject to basis-set superposition error (BSSE) because we use atom-centered Gaussian basis sets. This effect can be quite significant in proteinligand models containing hundreds of atoms, especially when the ligand is large. In protein-ligand models with ∼ 300 atoms, for example, BSSE effects up to ∼ 50 kcal/mol have been documented when double-ζ basis sets are used, as quantified by the difference between counterpoise-corrected and uncorrected values of ∆E int . Versions of counterpoise correction designed for use with MBE(n) have been reported but are not yet implemented in Fragme∩t, although that work is underway. In lieu of counterpoise correction, we will consider the use of larger basis sets in order to evaluate the importance of BSSE.