We also report substantial performance disparities for lysine residues in Amber14SB , which are caused by the partial charge assignment of the backbone and for which corrections already exist . Furthermore, we demonstrate the ability of our pmx-based approach to accurately resolve the pH-dependent pK a values of coupled residues, expanding the potential use to probing amino acids involved in unique redox or catalysis reactions. The average unsigned error (AUE) of the pmx computed pK a values across the residue classes considered was 0.68 ± 0.05 pK. The open-source pmx tool is freely available at deGrootLab/pmx.