Docking Tools

Docking Tools

Use this skill when the user asks to:

• dock a ligand, compound, or drug against a receptor
• estimate binding poses or affinities
• inspect a binding site or ligand contacts
• render docking poses or interaction figures
• batch-screen ligands and summarize docking rankings

DrugClaw does not ship a native docking engine module. This skill packages a reusable non-GUI docking workflow into a CLI template under templates/.

Runtime Requirements

The workflow assumes the runtime provides:

• obabel
• vina
• pymol
• pdbfixer for receptor cleanup and protonation
• Python modules used by the fuller docking and downstream chemistry workflow: openbabel, deepchem, pdbfixer, pyscf, rdkit, psutil, rsa, bs4, requests, pandas, matplotlib, seaborn, sklearn, Bio

Check first:

which obabel vina pymol pdbfixer || true
vina --version || true
obabel -V || true
python3 - <<'PY'
mods = ["openbabel", "deepchem", "pdbfixer", "pyscf", "rdkit", "psutil", "rsa", "bs4", "requests", "pandas", "matplotlib", "seaborn", "sklearn", "Bio"]
for name in mods:
    try:
        __import__(name)
        print(f"{name}: ok")
    except Exception as exc:
        print(f"{name}: missing ({exc})")
PY

If these tools are missing, say so immediately. Prefer the unified science sandbox image documented in docker/drug-sandbox.Dockerfile and docs/operations/science-runtime.md.

Preferred Workflow

Use the bundled template instead of rebuilding the pipeline ad hoc.

Bundled assets:

• templates/docking_workflow.py
• templates/docking_manifest.example.json
• templates/README.md

The template ports these usable desktop-tool capabilities into DrugClaw:

• ligand download from PubChem, ChEMBL, ZINC, TCMSP, local DrugBank exports, and the online DrugBank discovery API
• receptor download from RCSB PDB, AlphaFold DB
• SMILES and sequence-driven structure generation
• receptor preprocessing with pdbfixer -> obabel
• ligand preprocessing with 2D-to-3D generation, forcefield minimization, and biomolecule fallbacks
• automatic search-box inference from co-crystal ligands, active residues, or bounding boxes
• batch AutoDock Vina docking
• PDBQT-to-PDB complex assembly while preserving ligand coordinates
• CSV, heatmap, evaluation note, and paper-style markdown report generation
• optional PyMOL rendering for top hits
• optional heuristic ML rescoring when descriptors are available
• optional downstream DeepChem featurization or PySCF sanity checks outside the core docking pipeline
• optional chemistry post-processing with ADMET, ligand-only QSAR models, structure-aware affinity scoring, and virtual-screen reranking through chem-tools
• direct handoff from docked complexes into chem-tools/templates/protein_ligand_affinity.py for structure-aware affinity scoring

Scope boundary:

• port the computational workflow
• do not port the original GUI, installer wizard, or license/device-fingerprint logic

Fast Start

From the skill directory or a copied template workspace:

python3 templates/docking_workflow.py init-manifest -o docking_manifest.json
python3 templates/docking_workflow.py doctor --manifest docking_manifest.json
python3 templates/docking_workflow.py run --manifest docking_manifest.json

doctor now fails on dependencies that the current manifest actually requires. Use --strict when you also want optional plotting and chemistry extras audited. If the manifest uses drugbank ligands or chem_postprocess, the sibling chem-tools/templates bundle must also be present; doctor now checks that explicitly.

Incremental execution:

python3 templates/docking_workflow.py fetch --manifest docking_manifest.json
python3 templates/docking_workflow.py prepare --manifest docking_manifest.json
python3 templates/docking_workflow.py box --manifest docking_manifest.json
python3 templates/docking_workflow.py dock --manifest docking_manifest.json
python3 templates/docking_workflow.py analyze --manifest docking_manifest.json
python3 templates/docking_workflow.py render --manifest docking_manifest.json --top-n 5

Manifest Guidance

Use templates/docking_manifest.example.json as the base.

Supported input styles include:

• ligand source: smiles, local, pubchem, chembl, zinc, tcmsp, drugbank, auto
• receptor source: local, pdb, alphafold, peptide, protein, protein_sequence, nucleic, nucleic_sequence, auto

For drugbank ligands, set either settings.drugbank_catalog to a local DrugBank CSV, TSV, JSON, or XML export, or configure settings.drugbank_api_key / settings.drugbank_api_token for online lookup. The fetch stage will save both the exported structure and a per-drug JSON property file under inputs/ligands/.

Manual box override example:

{
  "box": {
    "mode": "manual",
    "center": [10.5, -3.2, 22.1],
    "size": [24, 24, 24]
  }
}

If box is omitted, the template tries:

1. co-crystal ligand coordinates
2. active-site residue coordinates
3. whole-structure bounding box

Optional chemistry post-processing block:

{
  "chem_postprocess": {
    "enabled": true,
    "run_admet": true,
    "run_virtual_screen": true,
    "affinity_model": "./models/affinity.joblib",
    "structure_affinity_model": "./models/protein_affinity.joblib",
    "bioactivity_model": "./models/bioactivity.joblib",
    "affinity_direction": "higher-better",
    "top_n": 25,
    "weights": {
      "affinity": 0.35,
      "activity": 0.35,
      "admet": 0.20,
      "docking": 0.10
    }
  }
}

When this block is enabled, analyze also writes ligand-level chemistry outputs under results/analysis/chem/.

Working Principles

• Create a dedicated working directory such as ./docking/.
• Keep the manifest, generated configs, logs, and renders together for reproducibility.
• Tell the user whether the search box came from prior knowledge, co-crystal geometry, active residues, or a geometric fallback.
• Treat docking scores as ranking heuristics, not experimental truth.
• When the pipeline falls back from protein-specific cleanup to generic conversion, report that explicitly.

Output Layout

The template writes:

• inputs/
• prepared/
• configs/
• results/docking/
• results/complexes/
• results/renders/
• results/analysis/
• metadata/session.json
• metadata/history.jsonl

Key deliverables:

• results/analysis/docking_summary.csv
• results/analysis/binding_energy_matrix.csv
• results/analysis/ligand_best_scores.csv
• results/analysis/binding_energy_heatmap.png
• results/analysis/evaluation.md
• results/analysis/paper_report.md
• results/analysis/ml_scores.csv when the ML stage is available
• results/analysis/chem/ when chemistry post-processing is enabled
• inputs/ligands/*.drugbank.json when DrugBank-backed ligands are used

Failure Modes

• obabel missing: cannot prepare receptor or ligand
• vina missing: cannot score poses
• pdbfixer missing: protein receptor cleanup falls back poorly; say so explicitly
• no settings.drugbank_catalog and no settings.drugbank_api_key / settings.drugbank_api_token: DrugBank ligands cannot be resolved
• no plausible box definition: ask for catalytic residues, a co-crystal ligand, or approximate binding-site coordinates
• PyMOL missing: still return text results plus the generated .pml scripts
• chemistry models missing: keep docking outputs and skip the optional reranking stage explicitly
• structure-affinity model missing: keep docking outputs, ligand-only chemistry outputs, and skip structure-aware scoring explicitly

Recommended Response Pattern

I used the bundled docking workflow template to prepare the receptor and ligand, generate the docking box, run AutoDock Vina, and save the artifacts in `docking/`.
The top-ranked pose reports `-8.1 kcal/mol` in `results/analysis/docking_summary.csv`.
I also generated `evaluation.md`, `paper_report.md`, and a PyMOL render script for the top hits.
This is a docking ranking result, not a measured binding affinity; the main uncertainty is the search-box definition.