We evaluated each scoring function by computing the Pearson correlation coefficient, ρ p , between its predictions { ŷ } and the experimental values { y } of pK for the complexes in the test set. Confidence intervals were estimated at the 95% significance level using 10,000 bootstrapped samples of the predictions. The Mann-Whitney U test was used to compare the distribution of bootstrapped ρ p values to assess the significance of the differences in correlation coefficient between two scoring functions. We also performed a permutation test with 10,000 samples to assess the possibility that correlations arose by random chance.