SUBSEQ.BIO
DOCS-DIFFDOCK-L

DiffDock-L

Predict candidate small-molecule binding poses against a prepared protein structure.

Overview

  • Docking a drug-like ligand into a prepared receptor PDB.
  • Exploring pose hypotheses when a binding pocket is uncertain.
  • Generating starting poses for rescoring, relaxation, MD, or free-energy workflows.

Modes

ModeInput shapeWhen to use it
single_complex
Single Complex Default		 Uses one selected file/source when file parameters are present. Dock one small-molecule ligand against one prepared protein PDB.
batch_csv
CSV Batch		 Uses one selected file/source when file parameters are present. Dock many protein-ligand complexes from a DiffDock-format CSV.

Canonical Job Configuration

These are the fields exposed by the default job configuration for diffdock-l. They are also returned by GET /api/v1/program/params?program=diffdock-l and submitted as the params JSON object to POST /api/v1/job/submit.

ParameterTypeModesWhat it does
protein_structure
Protein PDB		 Structure file Single Complex Prepared protein structure for docking. DiffDock-L job form uses protein PDB inputs.
Required; Files: .pdb
ligand_input
Ligand Input		 Text Single Complex Use a molecule file when you already have ligand coordinates, or SMILES for a small molecule string.
Default: Ligand File; Options: Ligand File, SMILES
ligand_file
Ligand File		 Input file Single Complex RDKit-readable ligand file. SDF is preferred; MOL2 and MOL are also accepted.
Required; Files: .sdf, .mol2, .mol; Shown when ligand_input is Ligand File
ligand_smiles
Ligand SMILES		 Ligand text Single Complex SMILES string for a small-molecule ligand.
Required; Shown when ligand_input is SMILES
complex_name
Complex Name		 Text Single Complex Optional name used for the prediction folder and ranked pose files.
batch_csv
DiffDock CSV		 Input file CSV Batch CSV with complex_name, protein_path, and ligand_description columns. File paths should be relative to the selected input root.
Required; Files: .csv
candidate_poses
Candidate Poses		 Integer All modes How many ligand poses to sample and rank for each complex. More poses take longer.
Default: 10; Range: 1-100
Advanced configuration fields
ParameterTypeModesWhat it does
sampling_depth
Sampling Depth		 Text All modes Fast uses fewer denoising steps; Thorough spends more steps per pose.
Default: Standard; Options: Fast, Standard, Thorough
save_trajectory
Save Trajectory		 Yes/no All modes Write reverse-diffusion trajectory snapshots for generated poses.
Default: false

Outputs And Metrics

  • Ranked ligand pose SDF files.
  • Optional reverse-process trajectory files when trajectory saving is enabled.
  • DiffDock confidence is pose-quality confidence, not binding affinity. Inspect structures and rescore when decisions matter.

Common Examples

  • Single complex: prepared protein PDB plus curated SDF ligand, 10 candidate poses, Standard sampling.
  • SMILES input: use a single-line SMILES with stereochemistry when relevant.
  • CSV batch: one row per protein-ligand pair after the single-complex protocol is settled.

Example API params

{
  "mode": "single_complex",
  "protein_structure": "receptor.pdb",
  "ligand_input": "Ligand File",
  "ligand_file": "ligand.sdf",
  "complex_name": "receptor_ligand",
  "candidate_poses": 10
}

Caveats

  • DiffDock-L assumes a fixed protein structure and is not for protein-protein or protein-nucleic-acid docking.
  • Large flexible ligands, covalent docking, metalloprotein chemistry, missing cofactors, and wrong protonation states can lead to misleading poses.
  • Use known-ligand controls where possible.

Advanced Submit

Advanced submit is still available for direct program arguments through POST /api/v1/job/submit-advanced. Prefer canonical configuration unless you need exact low-level arguments or are reproducing a known command line.

  • Advanced submit can run DiffDock-L with custom inference arguments or CSV batches.
  • Keep receptor and ligand preparation consistent across comparisons.
curl -X POST https://subseq.bio/api/v1/job/submit \
  -H "Authorization: Bearer <api_key>" \
  -F program=diffdock-l \
  -F 'params={"mode":"single_complex","protein_pdb":"receptor.pdb","ligand_input":"Ligand File","ligand_file":"ligand.sdf","complex_name":"receptor_ligand","candidate_poses":10}'

Further Reading