The target fidelity of 0.1 × (3/2)k B T that was discussed in Section 3 .1 .2 is a stringent criterion posited with an eye toward ab initio molecular dynamics studies using fragmentation. That approach is complicated by the complexity of analytic gradients in the presence of charge embedding, and likely unnecessary since force fields or semi-empirical quantum chemistry can be used to better and (much) more efficiently sample the conformational space. Thus, it is worth asking what eventual purpose fragment-based ab initio calculations of protein-ligand binding will serve, and what level of accuracy and convergence is necessitated by that application. We do not have a simple answer to that question but it's probably safe to assume that for ML, one desires a method that accurately reflects the interaction potential for short-range protein-ligand interactions, e.g., to replace docking models or classical force fields. For that purpose, the highest-quality ab initio interac-tion energies may not be necessary and DFT or even semi-empirical calculations might suffice.