In the AA simulations, Coulomb interactions were modeled with the smooth PME method with a real-space cut-off of 1.2 nm and a grid spacing of 0.14 nm, while Lennard-Jones interactions were smoothly switched to zero in range from 1.0 to 1.2 nm. In the CG simulations, Coulomb interactions were modeled by a Reaction Field potential with a 1.1 nm cut-off, r = 2.5, and RF = ∞, while Lennard-Jones interactions were truncated at 1.1 nm. To keep the temperature constant at 300 K, we used the v-rescale thermostat with time constants of 0.5 and 1.0 ps -1 for AA and CG simulations, respectively. The pressure was kept constant at 1 bar with the Parrinello-Rahman barostat 56 with relaxation times of 2.0 and 12.0 ps for AA and CG simulations, respectively. A leapfrog integrator was used with an integration steps of 2 an 20 fs for AA and CG simulations, respectively. In the AA simulations, the LINCS algorithm 57 was used to constrain bond lengths of the solutes, while the SETTLE algorithm was used to constrain internal degrees of freedom of the water molecules. Prior to the constant pH MD simulations, the potential energy of each system was minimized using the steepest descent method, followed by 1 ns of equilibration.