to def2-ma-QZVP. 3.1.1. Radial Enzyme Models. First, we study convergence of ∆E int with respect to the size of the enzyme model using both MBE(n) and conventional supramolecular calculations. We created reduced models of 181L (which has 2,636 total atoms) based on a simple radial cutoff around the benzene ligand, then computed ∆E int using each model for comparison to the result obtained using the complete 2,636-atom protein. (In followup work, we may consider the use of automated construction of binding-site models using residue interaction networks, 111-115 but here we use unsophisticated radial models as a simple means to establish protocols.) Figure shows how the results converge with respect to the size of the enzyme model, for both conventional supramolecular DFT and also for MBE (2) and MBE(3) approximations to it. Conventional calculations at the ωB97X-V/def2-ma-SVP level are converged using a model with 665 atoms, corresponding to all residues within 7 Å of the ligand. Resource limitations preclude ωB97X-V/def2-ma-TZVP calculations for models larger than this, but the convergence behavior for smaller models seems to mirror that obtained using the double-ζ basis set so we expect that ωB97X-V/def2-ma-TZVP calculations are also converged for the 665-atom model. Analogous testing was completed for 1LI2, which has phenol as a ligand, and the convergence behavior is very similar (Fig. ). In that case, a 7 Å (617-atom) model affords affords a converged value of ∆E int at the ωB97X-V/def2-ma-SVP level, while convergence of the ωB97X-V/def2ma-TZVP calculations looks similar.