We sought to test the robustness of our workflow using a set of new systems which were not used to select the "optimal" workflow parameters. We selected the Cyclophilin-D set from Alibay et al.'s study of ABFE in the fragment optimisation process. Excluding ligand 4 (because its affinity fell outside the SPR detection limits) produced a set of 9 fragments and merged molecules with a wide dynamic range. Alibay et al.'s results were re-analysed and plotted excluding this ligand in Section S21.