As an alternative to scaling all unit charges, we charge-scaled only the probed cysteine and balanced the missing negative charge by scaling the ions in solution. Computing the pK a values on the DsbA test set revealed a similar improvement trend as observed for global charge scaling, but nevertheless yielded a slightly poorer accuracy at a 0.7 scaling (Figure ). This difference is quite small and would seem to suggest that charge-scaled interactions of the probed cysteine itself and not that of other charged species is the major determinant of improved accuracy. In certain highly charged contexts (i.e., enzyme active sites), the accuracy improvement from charge-scaling other nearby residues is likely to play a larger role.