If not all residue types are available, the user will be prompted to manually provide the missing topologies. Currently, the GROMACS constant pH implementation only supports a modified version of the CHARMM36m force field, which includes dihedral modifications for improved sampling of the dihedral angles of the titratable groups. In addition to system-specific input, phbuilder reads from a global parameter file lambdagrouptypes.dat which stores the topology information of the titratable group types. The details of the lambdagrouptypes.dat organization and modification are discussed in the following sections. With the aforementioned input, phbuilder then generates the structure, topology, index and generic .mdp files required for running constant pH simulations. Scripts for the automation of titration and parameterization runs are also provided. phbuilder consists of three tools: gentopol, neutralize, and genparams, as presented in Figure . First, gentopol makes the residues selected by the user titratable, modifies the input structure file, and (re)generates the topology accordingly using gmx pdb2gmx.