In order to compare to other calculations we selected benchmark sets from previously published literature. Eight datasets originate from Wang et al. and contain the targets JNK1, TYK2, BACE, MCL1, CDK2, THROMBIN, PTP1B, and P38. Another eight datasets were assembled in the benchmark study of Schindler et al. Furthermore, we included protein-ligand systems that have appeared in various other FEP studies: GALECTIN-3 23 PDE2, 24 PDE10, 25 ROS1 26 and two additional BACE datasets. To keep our results as comparable as possible to prior calculations, we used the exact same input coordinates of the prepared systems as were previously used in the studies of Gapsys et al., Schindler et al. and Perez Benito et al. The input structures are provided in the protein-ligandbenchmark repository.