Further reducing the cutoff from 50% to 30% has a more apparent effect. Fig. shows similar behaviour when structures with test-set similar ligands are also excluded from the training set. As in the case where similar proteins are not excluded (Fig. ), the exclusion of structures containing test-set similar ligands has a consistently deleterious effect on the performance of all scoring functions, regardless of whether they make use of the RDKit descriptors. The performance of each scoring function on each of the 2007, 2013, and 2016 core sets, as well as bootstrapped 95%confidence intervals for the value of ρ p when training on the PDBbind 2018 refined set are included in the Supporting Information (SI Fig. ). For all scoring functions under all training and test scenarios, we reject the null hypothesis that the correlation between predicted and experimental affinity was due to random chance (permutation test p < 0.05).