…ature/docker-workflow

…mization

Detects missing residues in protein chains by checking residue numbering
discontinuities and C-N bond distances. Chains are split at gaps before
OpenMM minimization to prevent the creation of unrealistic peptide bonds
across gaps. Original chain IDs are restored after minimization.

- Add chain_gaps.py module with detect_chain_gaps, split_chains_at_gaps,
  and restore_chain_ids functions
- Integrate gap detection into relaxer.py relax() method
- Add split_chains_at_gaps config option (enabled by default)
- Add --no-split-gaps CLI flag to disable the feature
- Add comprehensive tests for chain gap detection

…atom

The bug was assigning a new chain ID for every atom at a gap start residue
instead of just once when entering a new segment. Added tracking of
processed gap starts to prevent duplicate chain assignments.

- Free up disk space by removing unused .NET, GHC, and Boost packages
- Install CPU-only PyTorch to avoid large CUDA dependencies
- Use --no-cache-dir to minimize pip cache usage

The GitHub Actions runner was running out of disk space when installing
PyTorch with CUDA dependencies (~5-7GB) alongside conda packages.

Co-Authored-By: Claude Opus 4.5 <noreply@anthropic.com>

…into idealize

Enable unconstrained minimization for protein-ligand complexes using
openmmforcefields for small molecule parameterization.

Changes:
- Add include_ligands, ligand_forcefield, and ligand_smiles config options
- Create ligand_utils.py module for ligand extraction and parameterization
- Add _relax_unconstrained_with_ligands method using SystemGenerator
- Update CLI with --include-ligands, --ligand-forcefield, --ligand-smiles
- Add [ligands] optional dependency group to pyproject.toml
- Add unit tests for ligand utilities
- Add ligand_utils.py to pylint exclude (optional dependency imports)

The implementation:
1. Separates protein (ATOM) and ligands (HETATM) from PDB
2. Processes protein with pdbfixer (avoiding terminal detection issues)
3. Parameterizes ligands with OpenFF Sage 2.0 (default) or GAFF2/Espaloma
4. Combines topologies and minimizes together

Usage:
  graphrelax -i complex.pdb -o minimized.pdb --include-ligands
  graphrelax -i complex.pdb -o minimized.pdb --include-ligands \
    --ligand-forcefield gaff-2.11 --ligand-smiles 'LIG:c1ccccc1'

Requires: pip install graphrelax[ligands]

Co-Authored-By: Claude Opus 4.5 <noreply@anthropic.com>

…nary

Replace the large hardcoded SMILES dictionary with dynamic extraction
from PDB coordinates using RDKit bond perception:

- Rename get_common_ligand_smiles() to get_ion_smiles() (only ions need
  explicit SMILES since they're single atoms without bond info)
- Add is_single_atom_ligand() helper function
- Update create_openff_molecule() to try RDKit parsing first, then fall
  back to OpenFF PDB parsing, using ion lookup only for single atoms
- Update relaxer.py to use the new approach
- Update tests to reflect the refactored functions

This removes ~70 lines of hardcoded SMILES while making the code more
robust - it can now handle any ligand that RDKit can perceive bonds for.

Co-Authored-By: Claude Opus 4.5 <noreply@anthropic.com>

The ligand libraries (openmmforcefields, openff-toolkit, rdkit) are
only available via conda-forge, not PyPI. Instead of lazy imports,
use top-level try-except blocks with clear ImportError messages that
tell users exactly how to install the missing dependencies:

- ligand_utils.py: Check for openff-toolkit and rdkit at import time
- relaxer.py: Check for openmmforcefields at import time
- Both provide clear conda install commands with version numbers
- pyproject.toml: Updated comment with full conda install command
- cli.py: Removed optional dependency check (now handled at runtime)

Co-Authored-By: Claude Opus 4.5 <noreply@anthropic.com>

Resolved conflicts:
- README.md: Combined mamba installation docs with pre-idealize feature
- cli.py: Added both artifact removal flags and pre-idealize flags
- relaxer.py: Combined ligand_utils and idealize imports

Co-Authored-By: Claude Opus 4.5 <noreply@anthropic.com>

- Remove action="append" in favor of single comma-separated string
- Fix parsing logic to handle single string instead of list
- Add unit tests for --keep-ligand CLI argument parsing

Co-Authored-By: Claude Opus 4.5 <noreply@anthropic.com>

Code cleanup:
- Consolidate WATER_RESIDUES to artifacts.py (was defined in 3 places)
- Create shared check_gpu_available() in utils.py (was duplicated)
- Remove unused add_ter_records_at_gaps() from chain_gaps.py
- Remove unused _relax_direct() method from relaxer.py (~100 lines)
- Remove corresponding test class TestAddTerRecordsAtGaps

README update:
- Update --keep-ligand documentation to show comma-separated syntax

Total: ~180 lines of redundant code removed.

Co-Authored-By: Claude Opus 4.5 <noreply@anthropic.com>

- Remove requirements.txt (dependencies in pyproject.toml)
- Update test_relaxer_integration.py to use public API:
  - Use check_gpu_available() from utils instead of removed method
  - Use relax() with constrained=False instead of removed _relax_direct()

Co-Authored-By: Claude Opus 4.5 <noreply@anthropic.com>

- Make it clear that openmmforcefields, openff-toolkit, and rdkit
  are conda-forge only (like pdbfixer)
- Add ligand support installation command to PyPI section
- Reorganize dependencies table to show required vs optional

Co-Authored-By: Claude Opus 4.5 <noreply@anthropic.com>

- pdbfixer, openmmforcefields, openff-toolkit, and rdkit are now all
  required for installation
- Simplified installation instructions
- Removed "optional" labeling from dependencies table

Co-Authored-By: Claude Opus 4.5 <noreply@anthropic.com>

- Change idealization from opt-in (--pre-idealize) to opt-out (--no-idealize)
- IdealizeConfig.enabled now defaults to True
- Add --ignore-missing-residues flag to skip adding residues from SEQRES
- Add --overwrite flag to allow overwriting output files
- Preserve residue numbering with keepIds=True in PDB output
- Update README to reflect new default behavior

Co-Authored-By: Claude Opus 4.5 <noreply@anthropic.com>

- Add renumber_residues_sequential() to idealize.py to ensure sequential
  residue numbering (1, 2, 3...) per chain after pdbfixer adds missing
  residues. This fixes false chain gap detection caused by non-sequential
  numbers from pdbfixer.
- Add CLI warning when using resfile with idealization enabled, since
  residue numbers in the resfile must match the idealized structure
- Update README to document the residue renumbering behavior

Co-Authored-By: Claude Opus 4.5 <noreply@anthropic.com>

Fix bug where ligands were extracted before the ligand-presence check,
causing the ligand-aware minimization path to never be triggered.

Now for unconstrained minimization with ligands:
- Ligands are detected before any extraction
- Full PDB (with ligands) is passed to _relax_unconstrained()
- Ligands are parameterized via openmmforcefields and minimized
  together with the protein

For constrained minimization, ligands are still extracted and restored
unchanged since AmberRelaxation cannot handle arbitrary ligands.

This fixes protein-ligand clashes that occurred when the protein moved
during minimization while ligands stayed in their original positions.

Co-Authored-By: Claude Opus 4.5 <noreply@anthropic.com>

Update idealization pipeline to properly handle ligands:

1. Add missing residues and atoms (protein only)
2. Idealize bond lengths and angles
3. Minimize protein with constraints (without ligands)
4. Reintroduce ligands and minimize protein+ligand complex together

This ensures ligands move with the protein during idealization rather
than staying at their original coordinates while the protein moves.

New function minimize_with_ligands() uses openmmforcefields to
parameterize ligands and perform constrained minimization on the
full protein-ligand complex.

Co-Authored-By: Claude Opus 4.5 <noreply@anthropic.com>

When ligands containing transition metals (heme, Fe-S clusters,
chlorophylls, etc.) are detected, raise a clear error explaining
the options instead of attempting to parameterize them.

- Add UNPARAMETERIZABLE_COFACTORS set in ligand_utils.py
- Add is_unparameterizable_cofactor() check function
- Update relaxer and idealize to fail early with helpful message

Co-Authored-By: Claude Opus 4.5 <noreply@anthropic.com>

Don't silently catch and continue when ligand parameterization fails
during idealization - let it fail with a clear error message instead
of failing later during relaxation.

Co-Authored-By: Claude Opus 4.5 <noreply@anthropic.com>

If create_openff_molecule() fails, let the error propagate rather
than silently skipping the ligand and then failing later.

Co-Authored-By: Claude Opus 4.5 <noreply@anthropic.com>