gromacs-workflow

GROMACS Workflow

Description

This skill covers end-to-end molecular dynamics simulations using GROMACS: topology construction and the .top/.itp hierarchy, .mdp parameter anatomy for energy minimization, NVT, NPT, and production runs, the grompp → mdrun → analysis pipeline, cutoff and PME setup, thermostat and barostat selection, constraint algorithms (LINCS, SETTLE), force-field compatibility (AMBER, CHARMM, OPLS-AA, GROMOS, Martini), HPC execution with MPI/OpenMP/GPU offload, and restart continuation. GROMACS is the standard tool for biomolecular and soft-matter simulations and is the reference code for AMBER, CHARMM36, and OPLS-AA force fields. Invoke this skill when setting up, running, diagnosing, or extending any GROMACS simulation.

Domain Context

GROMACS integrates Newton's equations of motion using a leap-frog Verlet integrator (the md integrator) or stochastic dynamics (sd). Its distinctive architecture separates the run-input file (.tpr, compiled from topology + mdp + coordinates by grompp) from the raw inputs (.top, .mdp, .gro), which means all simulation parameters are locked into the binary .tpr before mdrun starts. This compile-then-run model makes GROMACS simulations highly reproducible but requires re-running grompp whenever any parameter changes.

Several domain assumptions govern GROMACS applicability:

• Fixed topology: The bond list, angle list, dihedral list, and improper list are defined at the start of the simulation in the .top file and cannot change during the run. GROMACS is not a reactive MD code. Bond-breaking, proton transfer, and chemical reactions require reactive force fields (ReaxFF via PLUMED or an external code) or QM/MM.
• Classical nuclei: GROMACS integrates classical equations of motion. Zero-point energy and nuclear tunneling are ignored. For proton dynamics at low temperature, path-integral extensions (GROMACS + i-PI) are required.
• Long-range electrostatics are always present in biomolecular systems. Biomolecular and drug-like systems have partial charges on every atom. PME (Particle Mesh Ewald) is mandatory; a plain cutoff produces artifacts in electrostatic energy and forces that invalidate free energy calculations, solvation energies, and structural properties of charged systems.
• Force-field and water-model pairing is non-negotiable. AMBER ff14SB was parameterized with TIP3P; CHARMM36m with mTIP3P (a modified TIP3P with different LJ parameters). Using TIP4P with ff14SB or TIP3P with CHARMM36m introduces systematic density and structural errors that cannot be corrected by re-equilibration.
• GROMACS units: nm, kJ/mol, ps, K, bar. All .mdp distance parameters (rcoulomb, rvdw, rlist, box vectors) are in nanometres, not Ångströms. This is the single most frequent source of silently wrong input from users familiar with LAMMPS or AMBER.