with regard to the former, this performance was comparable to PropKa (0.63±0.22) (Figure ). We also found that CpHMD could accurately resolve the four aspartates within 0.5 pK. It is probable that both a limited training set and a less frequent dyad (i.e., a large difference in reference pK • a values) results in the markedly poorer estimate for C106 from PropKa.