where r 1 and r 2 are the locations of the two carbon atoms in the original C-C bond. The quantities R 1 = R 2 = 1.70 Å and R H = 1.1 Å are atomic van der Waals radii for carbon and hydrogen. This procedure is performed using Fragme∩t. Each of the ligands considered in this work is retained as a single fragment. For the large ligands in Fig. this may prove to be cost-prohibitive at levels of theory beyond DFT and will be revisited at a later time. In other applications of fragmentation to protein-ligand interaction energies, relatively small fragments have been used for both ligand and protein, so there is reason to expect that ligand fragmentation is viable. In the present work, however, our goal is to establish that the enzymatic host can be effectively fragmented in a systematic manner that is conducive to obtaining interaction energies that are converged with respect to both the size of the enzyme model (N ) and to the level of n-body interactions that are included. Fragmentation of the protein is relatively systematic whereas fragmentation of the ligand is less so, and we choose not to intermingle these two issues in the present work.