gromacs

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gromacs

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Knowledge base from "GROMACS Documentation Release 2026.2" by the GROMACS development team, enriched with Justin A. Lemkul's practical tutorial workflows and Chinese manual theory notes. Use when applying GROMACS for molecular dynamics simulations: system preparation, force field selection, ligand parametrization, .mdp parameter tuning, mdrun performance optimization, free energy calculations (alchemical + umbrella sampling), membrane protein simulation, virtual sites, trajectory analysis, and troubleshooting.

GROMACS Documentation Release 2026.2

Author: GROMACS development team | Enriched with: Justin A. Lemkul tutorials , Chinese manual (GROMACS 2019.6 中文译版) | Chapters: 40 | Generated: 2026-07-13

How to Use This Skill

• Without arguments — load core frameworks for reference
• With a topic — ask about PME, free energy, CGenFF, umbrella sampling, virtual sites, membrane simulation, or any indexed topic; I find and read the relevant chapter
• With chapter — ask for ch05, ch16, etc.; I load that specific chapter
• Browse — ask "what chapters do you have?" to see the full index
• Troubleshoot — describe your error or problem; I match it to known issues and solutions
• Practical workflow — ask for topic + "workflow" (e.g., "free energy workflow") for step-by-step tutorial examples

When you ask about a topic not covered in Core Frameworks below, I will read the relevant chapter file before answering.

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Core Frameworks & Mental Models

The GROMACS Simulation Pipeline

Use this 6-phase mental model for every simulation project:

1. System Preparation — pdb2gmx (topology) → editconf (box) → solvate (solvent) → genion (ions)
2. Energy Minimization — Remove steric clashes with steep integrator before any dynamics
3. NVT Equilibration — Stabilize temperature with v-rescale thermostat, position restraints on solute
4. NPT Equilibration — Stabilize density with Parrinello-Rahman barostat, release restraints gradually
5. Production MD — Remove restraints, run with appropriate thermostat/barostat
6. Analysis — trjconv -pbc mol -center first, then rmsd, rmsf, gyrate, hbond, energy, cluster, rdf, msd

Force Field Selection Heuristic

• Proteins (general): AMBER99SB-ILDN with TIP3P water — most validated
• Proteins + Lipids: CHARMM36 with TIP3P water — best lipid parameters
• Simple/united-atom: GROMOS54A7 with SPC water — computationally lighter
• Small organic molecules: OPLS-AA/L — good liquid properties
• Rule: Water model must match force field. Never mix.

Thermostat/Barostat Decision Matrix

Phase	Thermostat	Barostat	Why
EM	none	none	Minimization, no dynamics
NVT (initial)	Berendsen, tau-t=0.1	none	Fast convergence, wrong ensemble OK
NVT (equilibration)	V-rescale, tau-t=0.1	none	Correct NVT ensemble
NPT (equilibration)	V-rescale, tau-t=0.1	Berendsen, tau-p=2.0	Fast box relaxation
NPT (production)	V-rescale or Nose-Hoover	Parrinello-Rahman, tau-p=5.0	Correct NPT ensemble
SD production	SD integrator, tau-t=2.0	Parrinello-Rahman	Langevin, correct NVT

Timestep Selection

• 1 fs: No constraints, flexible water — rarely needed
• 2 fs: constraints=h-bonds — standard, use this
• 4 fs: HMR (mass-repartition-factor), constraints=h-bonds — with caution
• 5 fs: Virtual sites, constraints=all-bonds — specialized

PME Tuning Rule

Set rcoulomb = rvdw = rlist, fourierspacing = 0.12 nm, pme-order = 4.

• This is the standard that works for 99% of simulations.
• For GPU-resident mode: use constraints=h-bonds (not all-bonds).
• For PME-heavy systems: enable MTS (mts=yes, mts-level2-forces=longrange-nonbonded, mts-level2-factor=2).

Box Selection Principle

Use a rhombic dodecahedron (-bt dodecahedron) for all spherical solutes.

• Saves 29% solvent vs cubic box at same image distance.
• Use cubic only for crystalline systems or simple setups.
• Use -c -d 1.0 (center molecule, 1.0 nm minimum distance to box edge).

Performance Optimization Priority

1. Single precision (default) — double only for normal mode analysis
2. New GCC compiler — use latest version
3. GPU acceleration — -DGMX_GPU=CUDA (NVIDIA) or HIP (AMD)
4. GPU-resident mode — requires constraints=h-bonds, verlet scheme
5. Rhombic dodecahedron box — 29% fewer solvent atoms
6. MTS — evaluate PME every 2nd step
7. PME rank tuning — gmx tune_pme -s topol.tpr
8. Domain decomposition — ~500 atoms/core minimum

Free Energy Calculation Strategy

• Alchemical (TI/FEP): For binding/solvation free energies. Always discharge Coulomb first, then decouple vdW. Use soft-core (sc-alpha=0.5, sc-power=1, sc-sigma=0.3), 20+ lambda windows (Δλ≈0.05), analyze with BAR/MBAR. Two-stage hydration FE: ΔG_hydr = ΔG_coul + ΔG_vdW.
• Umbrella sampling (pull code): For PMF along 1-2 coordinates. Pulling→extract frames→umbrella windows→WHAM. Verify histogram overlap. pull-coord1-k ≈ 1000, window spacing ~0.1 nm.
• AWH: Adaptive, automatic. Best for 1-3 CVs. No post-processing needed.
• Expanded ensemble: For sampling multiple lambda states in one simulation.
• Replica exchange: For overcoming energy barriers. Temperature or Hamiltonian exchange.

Ligand Parametrization Decision Tree

• CHARMM force field: CGenFF server → penalty scores <10 = reliable, 10–50 = validate, >50 = reparametrize
• AMBER/GAFF: Antechamber + acpype
• GROMOS: ATB (Automated Topology Builder)
• OPLS: LigParGen (Jorgensen group)
• Rule: #include "ligand.itp" MUST appear after parent force field include and before first [ moleculetype ]

Membrane Simulation Rules

• Semi-isotropic pressure coupling mandatory for bilayers: pcoupltype = semiisotropic
• Separate COM motion removal: group membrane+protein separately from water+ions
• Temperature coupling: tc-grps = Protein_Lipid Water_and_ions — never couple lipids or ions separately
• Simulate above lipid Tm: DPPC ≥ 323 K (Tm = 315 K), DMPC ≥ 297 K, POPC ≥ 271 K
• Area per lipid validation: DPPC experimental ~62–64 Ų

Virtual Sites for Large Timesteps

• Transfer mass from eliminated atoms to parent atoms
• Function types: 2=linear, 3=planar, 4=tetrahedral
• With vsites: constraints=all-bonds, dt=5 fs
• HMR (easier alternative): dt=4 fs with constraints=h-bonds

Constraint Algorithm Selection

• LINCS (default): Fast, parallelizable, order 4. Use for all bonds.
• SHAKE: Iterative, slower. Use only when LINCS fails.
• SETTLE: Analytical for 3-atom water. Auto-applied for rigid water models.

Error Diagnosis Heuristic

• "LINCS warnings" → Bad geometry or too large dt. Check starting structure, reduce dt.
• "non-zero total charge" → Missing counterions. Use gmx genion -neutral.
• "Atom ... not found in ..." → Wrong topology/force field. Check GMXLIB.
• Temperature drifting → Check thermostat (PR barostat + Nose-Hoover need proper coupling).
• PME load imbalance → Wrong PME rank count. Use gmx tune_pme.
• Neighbor list overflow → Increase rlist buffer or set verlet-buffer-tolerance=-1.
• Segfault at start → Wrong GMX_SIMD for CPU architecture.
• WHAM fails to converge → No histogram overlap between umbrella windows. Decrease spacing or increase k.

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Chapter Index

All 40 chapters include comprehensive Chinese terminology, concepts, and formulas from GROMACS 2019.6 中文译版.

#	Title	Key Content
ch01	Downloads	Source code, regression tests
ch02	Installation Guide	CMake, compilers, FFTW, GPU backends
ch03	Known Issues	ROCm, GCC POWER9, oneAPI, SVE
ch04	Getting Started	Flow chart, file types, environment
ch05	System Preparation [+tutorial]	Full pipeline, worked example: Lysozyme 12-step workflow (Lemkul)
ch06	Managing Long Simulations	Checkpoints, reproducibility, restarts
ch07	FAQs	Installation, prep, methodology, analysis
ch08	Force Fields [+tutorial]	AMBER/CHARMM/GROMOS/OPLS, ligand parametrization (CGenFF), force field modification
ch09	MDP Parameters	Integrators, dt, cutoffs, coupling, constraints
ch10	Useful mdrun Features	Re-run, multi-sim, reproducibility
ch11	Performance Tuning	GPU, MPI, domain decomposition, MTS
ch12	Common Errors [+tutorial]	pdb2gmx/grompp/mdrun diagnostics, membrane/ligand/FE/umbrella troubleshooting
ch13	Command-Line Reference	All gmx tools with flags and usage
ch14	Terminology	MDP option glossary, GROMACS terms
ch15	Validation	Experimental features, pending validation
ch16	How-To Guides [+tutorial]	Solvation, membrane protein (InflateGRO), parameterization, biphasic systems
ch17	Preface & Introduction	Citation, free software, MD intro, Chinese terminology
ch18	Definitions & Units	Notation, MD units, precision
ch19	Algorithms: PBC & MD	Box types, neighbor searching, integrators
ch20	Algorithms: Constraints & Coupling	LINCS/SHAKE/SETTLE, thermostats, barostats
ch21	Algorithms: Free Energy [+tutorial]	TI/FEP/BAR/REMD/EM, practical FE workflows
ch22	Algorithms: Parallelization	Domain decomposition, GPU, load balancing
ch23	Non-bonded Interactions	LJ/Buckingham/Coulomb/PME/cutoffs
ch24	Bonded Interactions	Bonds, angles, dihedrals, restraints
ch25	Advanced Interactions [+tutorial]	Soft-core, LJ-PME, virtual sites construction (CO₂)
ch26	Topologies	.top/.itp structure, force field files
ch27	File Formats	.gro, .pdb, .tpr, .xtc, .edr, .cpt, .ndx
ch28	Special: Free Energy & Pulling [+tutorial]	PMF, umbrella sampling workflow (4 steps: pull→extract→windows→WHAM)
ch29	Special: AWH & Enhanced Sampling	AWH, enforced rotation, electrophysiology
ch30	Special: Advanced Methods	QM/MM, PLUMED, Colvars, NNP, FMM
ch31	Run Parameters & Programs	File types, program workflow
ch32	Analysis [+tutorial]	RMSD/RMSF/RDF/MSD/hbond/clustering, analysis workflow
ch33	Implementation Details	Virial, optimizations
ch34	Averages & Fluctuations	Formulae, implementation
ch35	Bibliography	Key references
ch36	Developer Guide	Contributing, coding standards
ch37	Doxygen Documentation	API reference
ch38	Release Notes	2026.2 changes
ch39	Advanced MDP Parameters	Free energy, AWH, pull, expanded ensemble
ch40	Tutorials & Resources	Training materials, references

Topic Index

• Area per lipid → ch16
• AWH → ch29, ch39
• BAR → ch21, ch32
• Berendsen → ch20
• Biphasic systems → ch16
• Box types → ch19
• CGenFF / Ligand parametrization → ch08
• CHARMM → ch8, ch26
• Checkpoint (.cpt) → ch6, ch27
• Chinese terminology / 中文术语 → all 40 chapters
• Chinese theory / 中文理论 → ch17-ch32, ch39 (comprehensive theory chapters)
• 中文关键词 → 参见各章中文术语对照表
• CGenFF penalty scores → ch08
• CMake → ch2
• Colvars → ch30
• COM motion removal (membrane) → ch16
• Constraints (LINCS/SHAKE/SETTLE) → ch20, ch9
• CUDA → ch2, ch11
• Cutoffs → ch23, ch9
• Decoupling (vdW, Coulomb) → ch21
• Deuterium order parameters → ch16
• Domain decomposition → ch22
• Double precision → ch18
• Energy minimization → ch21, ch9
• Error diagnosis → ch12
• Ethanol hydration FE → ch21
• Expanded ensemble → ch21, ch39
• FAQs → ch7
• File formats → ch27
• Force field modification → ch08, ch16
• Force fields (AMBER/CHARMM/GROMOS/OPLS) → ch8, ch25
• Free energy (FEP/TI/BAR) → ch21, ch25, ch28, ch39
• GPU acceleration → ch11, ch2
• grompp → ch13
• HMR (mass repartitioning) → ch25
• Hydrogen bonds → ch32
• InflateGRO → ch16
• insert-molecules → ch16
• Installation → ch2
• Integrators (md/sd/bd/steep/cg) → ch9, ch19
• Ions → ch5, ch16
• Lambda schedule → ch21
• LINCS → ch20
• Lipid phase transition (Tm) → ch16
• LJ-PME → ch25
• MDP parameters → ch9, ch39
• mdrun → ch10, ch11, ch13
• Membranes → ch16
• Methane FE tutorial → ch21
• MPI → ch2, ch22
• MTS (Multiple Time Stepping) → ch9, ch11
• Neighbor list → ch19, ch23
• Neural Network Potentials → ch30
• Nose-Hoover → ch20
• NPT → ch20
• NVT → ch20
• OpenCL → ch2, ch11
• OpenMP → ch22
• Parrinello-Rahman → ch20
• pdb2gmx → ch13
• Performance tuning → ch11
• PLUMED → ch30
• PME → ch25, ch9, ch19
• PMF (potential of mean force) → ch28
• Protein-ligand complex → ch08, ch05
• Pull code → ch28, ch39
• QM/MM → ch30
• Reaction coordinate → ch28
• Replica exchange → ch21
• Reproducibility → ch6, ch10
• RMSD/RMSF → ch32
• Semi-isotropic coupling → ch16, ch20
• Soft-core potentials → ch25, ch21
• Solvation → ch16
• System preparation → ch05 (includes full Lysozyme workflow)
• Temperature coupling → ch20, ch9
• Thermodynamic Integration → ch21
• Timestep → ch9, ch25
• Topology (.top/.itp) → ch26
• Trajectory (.xtc/.trr) → ch27
• tune_pme → ch11
• Tutorials → ch40
• Umbrella sampling → ch28 (includes full 4-step workflow)
• Validation → ch15
• Velocity Verlet → ch19
• Virtual sites → ch25 (includes CO₂ construction example)
• V-rescale → ch20
• Water deletor → ch16
• WHAM → ch28

Supporting Files

• glossary.md — all key GROMACS terms (~130 terms, with tutorial + Chinese additions)
• patterns.md — all workflows and design patterns (20+ patterns, including tutorial workflows)
• cheatsheet.md — quick reference: decision rules, tutorial commands, analysis commands, troubleshooting

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Scope & Limits

This skill covers the GROMACS 2026.2 manual content, enriched with:

• Justin A. Lemkul's practical tutorials — workflow examples integrated into relevant chapters (ch05, ch08, ch16, ch21, ch25, ch28, ch32)
• Chinese manual (GROMACS 2019.6 中文译版) — comprehensive Chinese terminology, theoretical exposition, formulas, and concepts integrated into all 40 chapters

For hands-on implementation, combine with actual GROMACS command execution (Bash). For force field-specific details beyond what's covered, consult the force field's original publications. Tutorial content from mdtutorials.com is provided under CC-BY 4.0 by Justin A. Lemkul. For topics beyond this skill, check the GROMACS website (https://www.gromacs.org) or the GROMACS user forum (https://gromacs.bioexcel.eu).