phbuilder: a tool for efficiently setting up constant pH molecular dynamics simulations in GROMACS

Constant pH molecular dynamics (MD) is a powerful technique that allows the protonation state of residues to change dynamically, thereby enabling the study of pH-dependence in a manner not possible before. Recently, a constant pH implementation was incorporated into the GROMACS MD package. Although this implementation provides good accuracy and performance, manual modification and preparation of simulation input files is required, which can be complicated, tedious, and error-prone. To simplify and automate the setup process, we present phbuilder, a tool that automatically prepares constant pH simulations for GROMACS by modifying the input structure and topology as well as generating the necessary parameter files. phbuilder can prepare constant pH simulations from initial protein structures as well as by converting existing simulation runs. phbuilder also provides functionality for performing titrations and parameterizing new titratable group types. The tool is freely available at www.gitlab.com/gromacs-constantph. We anticipate that phbuilder will make constant pH simulations easier to set up and thereby more accessible to the GROMACS user community.