We rescaled all full unit charges (i.e., charged side chains and ions) (Figure ) on the interval [0.60, 1.00] with a 0.05 increment in CHARMM36m and recomputed the pK a values of the DsbA test set. CHARMM36m was chosen because of its higher accuracy in predicting cysteine pK a and because recent charge scaling efforts have successfully employed this force field. We observed the accuracy saturated to an AUE of 1.42 ± 0.14 pK for a scaling of 0. ). Accounting for residue coupling improved the accuracy of CHARMM36m-ECC even further, shifting the overall AUE from 1.78 ± 0.21 pK to 1.61 ± 0.21 pK (Figure ). Compared to plain CHARMM36m, CHARMM36m-ECC did not significantly improve the already strong histidine pK a prediction performance (i.e., 0.69±0.16 pK vs 0.71±0.16 pK). Charge-scaling did also not completely resolve the significant pK a underestimation observed for YopH tyrosine phosphatase (PDB: 1YPT) (Figure ). While we could exactly reproduce the relative effects of two nearby mutations (Figure ), the absolute pK a values were downshifted by ≈ 4 pK units (Figure ).