To run the SepTop calculations for this BACE1 dataset, we created ligand maps performing transformations both within each series as well as transformations spanning across different series. We ran 10 transformations for the six ligands within each series and 5 transformations between each series pair, giving a total of 45 transformations. Some transformations within a series were also scaffold hopping transformations, such as ring extensions, and we manually created the perturbation map to include both challenging transformations and transformations involving smaller R-group changes.