phbuilder: A Tool for Efficiently Setting up Constant pH Molecular Dynamics Simulations in GROMACS

Area of Science:

• Computational Chemistry
• Biophysics
• Molecular Modeling

Background:

• Constant pH molecular dynamics (MD) enables dynamic changes in residue protonation states, crucial for studying pH-dependent phenomena.
• The recent integration of constant pH MD into GROMACS offers enhanced accuracy and performance.
• However, manual setup of GROMACS constant pH simulations is complex, time-consuming, and error-prone.

Purpose of the Study:

• To develop an automated tool, phbuilder, for simplifying the setup of constant pH MD simulations in GROMACS.
• To enhance the accessibility and ease of use of constant pH MD for the GROMACS community.

Main Methods:

• phbuilder automatically modifies input structures and topologies for GROMACS.
• It generates necessary parameter files for constant pH simulations.
• The tool supports simulations from initial structures or existing systems and includes titration/parametrization functionalities.

Main Results:

• phbuilder successfully automates the preparation of constant pH MD simulation input files.
• The tool streamlines modifications to structures, topologies, and parameter files.
• Functionality for titrations and single-site parametrizations of novel titratable groups is integrated.

Conclusions:

• phbuilder significantly simplifies and automates the setup of constant pH MD simulations in GROMACS.
• This automation makes advanced pH-dependent molecular dynamics studies more accessible to a wider range of users.
• The tool is freely available, promoting broader adoption within the GROMACS user community.