Computationally, we also have access to the whole set of pK a solutions which are not necessarily limited by this Hesenderson-Haselbalch relation. We can combine Equations 3 (in the main text) and 25 and compute these pK a values at various pH: ). The singly protonated probabilities are indicated with dashed-dotted lines. Vertical spans indicate experimental pK a values and uncertainties (note that D83 has a pK a < 2.2). Error bands were bootstrapped. In the case of E18, CpHMD simulations were run with C106 protonated (C H ) or deprotonated (C -).