The analysis workflow used for analyzing the calculations is available in Hahn et al. The statistics in this workflow were calculated using Arsenic (repackaged as Cinnabar), which is a package implementing best practices for consistently calculating statistics and reporting results from binding free energy calculations. The test set consisted of 22 different series of congeneric ligands binding to 20 protein targets with a total of 599 ligands. All calculations used the input structures provided in the protein-ligand-benchmark repository. More detailed discussion of the workflow, the employed parameters, analysis and benchmark sets can be found in the Supporting Information.