Recently, FEP+ was used to compute the pK a values of 79 aspartate and glutamate residues . We observed comparable performance on the overlapping 65 residue dataset (referred to as the FEP+ dataset); the average unsigned error was 0.65 ± 0.08 for NEQ and 0.61 ± 0.07 for FEP+ (Figure ), and the Pearson correlation coefficients were 0.74 ± 0.06 and 0.80 ± 0.09, respectively. These represented the two strongest performing methods on the FEP+ dataset. We also assessed the degree of correlation between the ∆pK a estimates for both methods; here, the Pearson correlation coefficient was 0.83 ± 0.05 suggesting a strong relationship (Figure ). This was the second strongest correlation between any two methods on the FEP+ dataset. Regarding residues, glutamate pK a values were predicted with higher accuracy than aspartate (Figure ).