Parameterization of titratable groups is one of the critical steps for accurate constant pH simulations. The original way to compute the correction potential V MM is based on thermodynamic integration (TI). However, TI can be inefficient and lead to an inaccurate fit of To avoid these issues, we propose a new two-step scheme for the parameterization of titratable groups. First, we run fast but not so accurate TI to get an approximated fit of V MM , and next, we reweigh V MM based on the long sampling simulations of the group simulated at pK a =pH and biasing barrier set to 0. At such conditions, the distribution of λ-coordinate should be flat if V MM is fitted accurately (Figure ). However, after a fast TI step, this might not be the case. For example, for arginine, the distribution of λcoordinates obtained from sampling runs with V MM coefficients calculated based on a fast TI parameterization were skewed towards λ = 0. From those simulations the correction to the V MM can be calculated using Boltzmann inversion: