This combinatorial growth can lead to catastrophic lossof-precision under some circumstances, and in some cases fragment-based calculations may be more expensive than the supramolecular calculation they are intended to approximate. In the present work, we use distancebased screening to reduce the number of subsystems for n > 2. Subsystems are eliminated if the minimum interatomic distance between any two fragments exceeds a specified threshold (R cut ) that we will vary systematically to test for convergence. In the case of 181L, where N frag = 164, setting R cut = 8 Å for MBE(3) reduces the number of subsystem calculations from 708,561 to 16,016, a 97.7% reduction. This makes higher-order n-body expansions feasible in large systems. Enzymatic reaction energies and barrier heights converge quickly with respect to R cut . Energy-based screening (e.g., with GFN2-xTB) can be even more efficient than distance-based screening but was not fully implemented in Fragme∩t when this work was undertaken.