Basis set trends are similar to what is observed for the T4-lysozyme data set, with a reduction in BSSE as the basis-set quality improves leading to a reduction in |∆E int |. Numerical values change much more dramatically than they did for the T4 lysozymes, however, because the much larger LIDS ligands engender larger BSSE, which increases with system size because the number of neighbor atoms increases. For example, swapping def2-ma-SVP for def2-ma-QZVP changes ∆E int by an average of 7.0 kcal/mol for the T4 lysozyme data set but for LIDS the change is a staggering 19.2 kcal/mol. For the large ligands, results obtained using the def2-ma-SVP basis set seem inappropriate to use. This is important information given that many DFT calculations of proteinligand interactions continue to use double-ζ basis sets for reasons of cost. Many-body counterpoise corrections may facilitate the use of double-ζ basis sets and we intend to explore this in future work.