In the atomistic simulations the multisite representation was used to model the protonation states of titratable residues. Two λ-coordinates were introduced to model the two forms of the carboxylic acid side chain in Asp and Glu, while three coordinates were used to describe the three protonation states of the imidazole sidechain in His. In the CG simulations, the single-site representation was used, in which the A and B states represent the protonated and deprotonated states of the titratable beads. Because, in contrast to AA force fields, there is no distinction between the two neutral forms of the His sidechain in the Martini force field, the single-site description for HIS suffices in the CG simulations. In both atomistic and coarse-grained simulations, the transformations between the different protonation states were achieved by changing the charges of the ionizable groups. The Lennard-Jones and bonded terms (bonds, angles, and torsions) were kept in the protonated and deprotonated state in AA and CG simulations, respectively (see Supplementary Information, Fig. ). We show in SI that the contribution of these terms is sufficiently small to be neglected without significant error. Note, that these terms can be made λ-dependent as well, but this is beyond the scope of the current work since the efforts to implement this are high.