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Add proteinbox workflow#15

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MSiggel wants to merge 14 commits into
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feature/protein-box
Open

Add proteinbox workflow#15
MSiggel wants to merge 14 commits into
mainfrom
feature/protein-box

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@MSiggel

@MSiggel MSiggel commented May 31, 2026

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Summary

  • add the proteinbox simulation type, models, workflow dispatch, and lysozyme example
  • add protein preparation through GROMACS pdb2gmx, including local force-field checks, exact disulfide prompts, and protonation overrides
  • add solvation, ionization, topology update, restrained OpenMM relaxation, and GROMACS run schedules for proteinbox builds
  • align GROMACS/pdb2gmx configuration with the existing CGenFF setup pattern through settings, config init, and config template updates
  • add focused tests for proteinbox models, metadata, topology parsing, disulfide/protonation behavior, force-field checks, and config handling

Tests

  • pytest mdfactory/tests/test_settings.py mdfactory/tests/test_sync_config_local_paths.py mdfactory/tests/test_proteinbox.py

Closes #13

MSiggel and others added 12 commits May 31, 2026 11:18
@MSiggel @claude
Add proteinbox models: ProteinSpecies, ProteinBoxComposition, Pdb2gmx…
2ffc0b3 
…Config

New models for the proteinbox simulation type:
- ProteinSpecies: PDB-path-based species with disulfide/protonation annotations
- ProteinBoxComposition: protein + box_padding + ionization config
- Pdb2gmxConfig: force field and water model config for pdb2gmx
- GromacsProteinParameterSet: output paths from pdb2gmx
- BuildInput extended with proteinbox type and pdb2gmx parametrization

Closes: relates to #13

Co-Authored-By: Claude Opus 4.6 <noreply@anthropic.com>
@MSiggel @claude
Add setup/protein.py: pdb2gmx wrapper, PDB cleaning, topology utilities
9d47492 
Functions for the proteinbox build pipeline:
- check_gmx_available: verify gmx binary is on PATH
- clean_pdb: PDBFixer-based PDB standardization
- run_pdb2gmx: subprocess wrapper for gmx pdb2gmx
- extract_charge_from_topology: parse net charge from .top/.itp
- update_topology_molecules: append water/ion entries to [ molecules ]
- validate_with_grompp: dry-run topology validation

Co-Authored-By: Claude Opus 4.6 <noreply@anthropic.com>
@MSiggel @claude
Add relax_with_protein_restraints() to openmm_utils.py
9eefb34 
Brief NPT equilibration with protein heavy atoms position-restrained
via CustomExternalForce. Allows water/ions to relax around the fixed
protein structure before GROMACS production runs.

Co-Authored-By: Claude Opus 4.6 <noreply@anthropic.com>
@MSiggel @claude
Add build_proteinbox() and wire up dispatch in workflows.py
496888d 
Build pipeline: clean PDB -> pdb2gmx -> center in cubic box -> solvate
(reuses existing solvate()) -> ionize (reuses ionize_solvated_system())
-> update topology -> OpenMM relax with protein restraints -> validate.

Co-Authored-By: Claude Opus 4.6 <noreply@anthropic.com>
@MSiggel @claude
Add proteinbox MDP run schedule files (CHARMM36m settings)
a405ace 
MDP files for protein-in-waterbox equilibration and production:
- em.mdp: steepest descent minimization
- nvt.mdp: NVT with -DPOSRES and Protein/Non-Protein tc-grps
- npt.mdp: NPT with -DPOSRES and Berendsen barostat
- md.mdp: production with Parrinello-Rahman, no position restraints

All use CHARMM36m-specific nonbonded settings (1.2nm cutoffs,
Force-switch VdW modifier, no dispersion correction).

Co-Authored-By: Claude Opus 4.6 <noreply@anthropic.com>
@MSiggel @claude
Track proteinbox MDP files (force-add past .gitignore *.mdp rule)
1c7fe01 
Co-Authored-By: Claude Opus 4.6 <noreply@anthropic.com>
@MSiggel @claude
Add proteinbox tests and example YAML
f03dc7c 
- 13 unit tests covering ProteinSpecies, ProteinBoxComposition,
  Pdb2gmxConfig, BuildInput integration, and topology parsing
- Fix ProteinSpecies to default count=1/fraction=1.0 at field level
  (avoids parent Species validator ordering issue)
- Example YAML for lysozyme with CHARMM36m force field

Co-Authored-By: Claude Opus 4.6 <noreply@anthropic.com>
@MSiggel @claude
Fix review findings: Path import, cwd paths, metadata, protonation
263cf54 
Addresses 4 P2 review comments:
- Add missing `from pathlib import Path` to build.py module scope
- Resolve all paths to absolute in run_pdb2gmx before subprocess call
  (avoids cwd confusion with output_dir)
- Add species/total_count/charge properties to ProteinBoxComposition
  and proteinbox case in BuildInput.metadata for analysis compatibility
- Implement _apply_protonation_states: renames residues in PDB before
  pdb2gmx so protonation overrides (HIS->HIE, GLU->GLH) are applied

Co-Authored-By: Claude Opus 4.6 <noreply@anthropic.com>
@MSiggel @claude
Add force field check, fix grompp cleanup, fix file handle leak
decb36d 
- Add check_forcefield_available() that verifies the force field directory
  exists in GROMACS share, GMXLIB, or cwd before invoking pdb2gmx. Lists
  available force fields on failure.
- Clean up mdout.mdp artifact in validate_with_grompp alongside check.tpr.
- Fix bare open() file handles in relax_with_protein_restraints (use with-blocks).
- Add CHARMM HIS alias translation (HIE→HSE, HID→HSD, HIP→HSP for charmm FFs).
- Use re.fullmatch for protonation state key parsing (reject trailing chars).
- Validate 3-character residue names for PDB column safety.
- Add disulfide bond prompt generation (_build_disulfide_prompt_input) for
  deterministic pdb2gmx -ss interaction.
- Resolve paths before working_directory context switch to avoid cwd breakage.

Co-Authored-By: Claude Opus 4.6 <noreply@anthropic.com>
@MSiggel @claude
Add force field registry with auto-download and fix charge parsing
c07392a 
- Add FORCEFIELD_REGISTRY mapping friendly names (charmm36m, charmm36m-ljpme)
  to MacKerell lab download URLs and extracted directory names.
- Auto-download missing force fields on first use from the registry.
  Stored in platformdirs user_data_dir (~/Library/Application Support/mdfactory/forcefields/).
- resolve_forcefield() translates friendly names to actual directory stems
  so users write "charmm36m" in YAML and pdb2gmx receives the correct
  directory name.
- Inject GMXLIB in subprocess env so gmx finds downloaded force fields.
- Fix extract_charge_from_topology: skip .ff/ library includes (ions.itp,
  tip3p.itp) that contain atom type templates, not system charges. Was
  causing +159 charge for lysozyme with charmm36m instead of +8.

Co-Authored-By: Claude Opus 4.6 <noreply@anthropic.com>
@MSiggel @claude
Add [gromacs] config section for gmx path and force field management
848041e 
- Add [gromacs] section to settings.py with GMX_PATH and FORCEFIELD_DIR,
  following the same pattern as [cgenff] SILCSBIODIR.
- Settings.__init__ auto-prepends FORCEFIELD_DIR to GMXLIB env var on
  startup, matching how SILCSBIODIR is auto-set for CGenFF.
- check_gmx_available() checks configured GMX_PATH first, falls back
  to PATH lookup.
- All gmx subprocess calls (pdb2gmx, grompp) use the configured binary
  and inject GMXLIB for force field resolution.
- Add GROMACS setup to config wizard (sync_config.py): prompts for gmx
  path, forcefield dir, and offers to download CHARMM36m on setup.

Co-Authored-By: Claude Opus 4.6 <noreply@anthropic.com>
@MSiggel
Align proteinbox gromacs configuration
4d0dd49
@MSiggel MSiggel mentioned this pull request May 31, 2026
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maxscheurer
maxscheurer requested changes Jun 1, 2026
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Comment thread examples/proteinbox/lysozyme_charmm36m.yaml
- [76, 94]
protonation_states:
HIS15: HIE
box_padding: 12.0

@maxscheurer maxscheurer Jun 1, 2026

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Consistent naming, as in other system types?

Comment thread examples/proteinbox/lysozyme_charmm36m.yaml
- [64, 80]
- [76, 94]
protonation_states:
HIS15: HIE

@maxscheurer maxscheurer Jun 1, 2026

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Should be a list of key-value pairs, right?

Comment thread examples/proteinbox/lysozyme_charmm36m.yaml
type: pdb2gmx
forcefield: charmm36m
water_model: tip3p
ignh: true

@maxscheurer maxscheurer Jun 1, 2026

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Bad key name, have no idea what that means.

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Add proteinbox simulation type with pdb2gmx backend

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@MSiggel @maxscheurer