We note that GNCA4-4 appears to be an outlier on this plot, with a D-A distance of >4.0Å and a D-H…A angle of ~130°. However, removing this variant still gives good correlations of R 2 = 0.68, and -0.64 for the correlation between the calculated activation free energies and to the calculated D-H distances and D-H…A angles, respectively. Finally, we also obtain good correlations between log kcat/KM and the calculated D-H distances and D-H…A angles, at R 2 = -0.71, and 0.71 respectively (Figure ).