Figure shows a plot of the similarity between the LEF and Enamine test/train splits. The similarity is calculated as the maximum similarity between all molecules of a test set to any molecule of the training set using the Dice similarity of fluorine fingerprints of length 7 (F-FP-7) and the Tanimoto similarity of extended connectivity fingerprints with a radius of 2 (ECFP4). The FFL-d6 (the Enamine test set) contains only very few molecules with a maximum F-FP-7 Dice similarity lower than 0.6 to molecules of the FDS-1000 (the Enamine training set). Tranche 2 (the LEF test set) on the other hand contains a substantial fraction of molecules with a maximum F-FP-7 Dice similarity lower than 0.6 to molecules of the LEF4000 (the LEF training set). A higher number of dissimilar molecules in tranche 2 suggests that this train/test split required more extrapolation.