for the three-body corrections. Truncating eq. 1 at nbody terms, we will denote the resulting approximation as MBE(n). Electrostatic embedding of the subsystem calculations, using classical point charges derived from the fragment wave functions, is often used in an effort to hasten convergence of the MBE. We avoid this, however, because we have found that charge embedding can lead to inconsistent convergence of the n-body expansion. The use of self-consistent point charges also significantly complicates the formulation of analytic energy gradients. Fragments I, J, K, . . . are taken to be individual amino acids of the enzyme (except where stipulated otherwise, for testing purposes), with the substrate as its own fragment. Although larger fragments have sometimes been used for proteins, we are able to achieve our target accuracy of 1 kcal/mol using mostly singleresidue fragments, except for the substrate whose treatment is discussed below. Alternatively, overlapping fragments have sometimes been used for polypeptides and proteins, which can be rationalized in terms of a generalized (G)MBE. To date, most overlappingfragment applications use a one-body approach that captures through-bond interactions but not through-space interactions. A two-body GMBE can capture both, but is relatively expensive in terms of the number of subsystems that are generated. As such, we stick to the simple MBE(n) approach in this work.