Boltz Workflow: Antiviral Protease

About lab

Boltz Workflow: Antiviral Protease

Antiviral Protease Workflow is a curated BioSimulant Boltz workflow. It runs a single curated target sequence and a single reference ligand SMILES through Boltz-2, then presents the predicted complex, binder probability, affinity-like value, confidence metrics, run metadata, and report-ready caveats in the standard Biosimulant lab interface.

The workflow is designed for learning, comparison against known examples, and early biological hypothesis generation. It is not experimental validation, a clinical prediction, or a replacement for docking review, MD/FEP, assay design, or wet-lab confirmation.

Workflow Status

This lab validates locally, exports as a portable .bsilab package, and has a successful private pre-publication GPU-backed run. It is published on Biosimulant Hub and now uses a multi-stage Compose graph. The graph separates source-backed context, input assembly, Boltz-2 prediction, conservative interpretation, and visual reporting.

Publication checklist:

manifest validation passes: complete
strict package export passes: complete
entrypoints import successfully: complete
unit tests pass: complete
at least one real GPU run completes: complete
run results include structure, affinity, confidence, metadata, and visuals: complete
screenshots/assets are captured from the real run: complete
Hub workflow card is public and points at the published lab id: complete

Pre-Publication Run Evidence

The current assets and metrics are derived from this private staged remote run:

run id: c40d2e2a-1466-482b-bfa5-d043fd36808b
staged lab id: b453b1a8-7411-4382-8f94-4cba4d54f681
run lab commit: 11a71ae65d8c11008c4faddeb74df2208de0cc11ddb184cb0348ebd5dd81d61b
remote size: GPU A10G
status: completed
duration: 420.7 seconds
credits settled: 35

Key outputs from the run:

affinity_probability_binary: 0.99848735332489
affinity_pred_value: -1.8409757614135744
confidence_score: 0.988286316394806
complex_plddt: 0.9863650798797609
iptm: 0.995971143245697
ligand_iptm: 0.995971143245697

Curated Known Example

The bundled known-example mode starts with:

target: SARS-CoV-2 3C-like main protease
target source: RCSB PDB 7VH8 sequence FASTA
ligand: Nirmatrelvir reference protease inhibitor
ligand source: PubChem CID 155903259
protein sequence length: 306 amino acids
MSA server usage enabled for the default example

The workflow is for computational exploration only and does not establish antiviral activity, dosing, safety, or clinical effect.

What This Workflow Does

When run, the workflow:

Builds a Boltz-2 request from the curated or user-supplied protein and ligand inputs.
Runs the Boltz-2 CLI on a GPU-backed runtime.
Parses the top-ranked structure artifact.
Parses Boltz-2 affinity and confidence summaries.
Emits Biosimulant visuals and report-ready outputs.

Compose Workflow Graph

The published workflow is intentionally split into real BioSimulant modules:

antiviral_target_context emits source-backed target, ligand, disease/use-case, provenance, and caveat context.
protease_ligand_setup resolves the public protein, ligand, MSA, and run-option inputs into the exact Boltz request.
boltz_boltz2_affinity_predictor runs the unchanged Boltz-2 scientific wrapper.
protease_prediction_interpreter converts raw Boltz outputs into conservative evidence fields without adding new biological claims.
visualisation renders the 3D structure, confidence/affinity summaries, source context, request traceability, and Q/A caveat cards.

This makes the Compose view match the workflow promise while keeping Boltz-2 as the only predictive scientific model. The surrounding modules are provenance, request assembly, interpretation, and presentation stages.

Inputs

protein_sequence: amino-acid sequence for the target protein. If omitted, the bundled known example is used.
ligand_smiles: SMILES string for the ligand. If omitted, the bundled known example ligand is used.
msa_path: optional path to a precomputed .a3m MSA file.
run_options: optional record for workflow/runtime options.

The known example mode works because lab.yaml defines defaults directly on the Boltz runner model. A new user can click Run without knowing YAML, SMILES formatting details, or Boltz CLI arguments.

Outputs

structure_artifacts: paths to the predicted complex structure files, usually mmCIF.
affinity_summary: affinity-style outputs parsed from Boltz-2.
confidence_summary: model confidence outputs for the top-ranked prediction.
run_metadata: execution metadata, output paths, captured logs, and status.

The visualisation model turns these records into standard Biosimulant run visuals, including a structure viewer and summary metrics.

Reading The Affinity Outputs

Boltz-2 distinguishes two affinity-oriented outputs that should not be collapsed into one meaning.

affinity_probability_binary is most useful as a binder-vs-decoy style signal. In product language, it is the binder probability. It is useful when comparing likely binders against unlikely binders under a hit-discovery framing.

affinity_pred_value is intended for ligand-optimization style use cases. In product language, it is an affinity-like value. It should be used cautiously and comparatively, not as a direct experimental measurement.

Both outputs are model predictions. They can help rank hypotheses for follow-up, but they do not prove binding, potency, selectivity, mechanism, or biological effect.

Reading The Structure

The structure viewer shows the predicted protein-ligand complex from the top-ranked Boltz output. Use it as a sanity check:

Is the ligand near a plausible pocket?
Is the interface confidence reasonable?
Does the pose look inconsistent with the score?
Are there warnings in run metadata?

A high binder probability with an implausible pose should be treated as suspicious. A plausible pose with weak confidence should also be treated as uncertain.

Safe Use Cases

This workflow is best for protease-inhibition concepts, antiviral target examples, and follow-up candidate list preparation.

Safe uses include:

Learn protein-ligand modeling workflows.
Compare known ligand examples.
Generate early hypotheses.
Prepare candidate lists for deeper review.
Create reproducible computational biology reports.
Teach structure-based drug-discovery concepts.

Do Not Claim

Validated drug discovery.
Clinical prediction.
Medical diagnosis.
Final compound selection.
Wet-lab replacement.
FEP replacement.
Experimentally guaranteed binding-affinity certainty.

Assets

The current screenshots were captured from the successful private pre-publication GPU run above, using its persisted mmCIF structure artifact and parsed run metrics.

Boltz-2 predicted protein-ligand complex structure

Boltz-2 affinity and confidence summary metrics

Implementation Notes

This workflow intentionally reuses the existing Boltz-2 affinity predictor and visualisation modules. The product difference is in the lab packaging:

guided disease or target context
workflow tags
known example defaults
safe input names
report-oriented caveats
future Hub placement in the Boltz Workflows section

Guided Boltz-2 workflow for exploring a viral 3C-like protease target with a nirmatrelvir reference ligand example, binder probability, affinity-like value, confidence metrics, and reproducible report context.

Runtime

Duration0.01

Comms Step0.01

Settle Steps1

Runs

Total0

Completed0

Failed0

Metadata

Packageboltz-workflow-antiviral-protease

Created2026-05-23

Updated2026-05-23

boltz-workflowboltzprotein-ligandaffinitystructural-biologyguided-workflowgpuantiviralproteasesars-cov-2contextprovenanceinput-assemblyinterpretationdockingvisualisationother

Manifest

{
  "io": {
    "inputs": [
      {
        "name": "protein_sequence",
        "label": "Target Protein Sequence",
        "maps_to": "protease_ligand_setup.protein_sequence",
        "description": "Amino-acid sequence for the curated SARS-CoV-2 3C-like protease target; maps directly to the Boltz-2 protein input."
      },
      {
        "name": "ligand_smiles",
        "label": "Nirmatrelvir Ligand SMILES",
        "maps_to": "protease_ligand_setup.ligand_smiles",
        "description": "SMILES string for the nirmatrelvir reference protease-inhibitor example; maps directly to the Boltz-2 ligand input."
      },
      {
        "name": "msa_path",
        "label": "Precomputed MSA Path",
        "maps_to": "protease_ligand_setup.msa_path",
        "description": "Optional path to a precomputed MSA file; leave unset when the configured Boltz MSA server is used."
      },
      {
        "name": "run_options",
        "label": "Boltz Run Options",
        "maps_to": "protease_ligand_setup.run_options",
        "description": "Optional structured controls for the Boltz workflow, including source metadata, sampling settings, and interpretation scope."
      }
    ],
    "outputs": [
      {
        "name": "scenario_context",
        "label": "Workflow Scenario Context",
        "maps_to": "antiviral_target_context.scenario_context",
        "description": "Source-backed target, ligand, use-case, provenance, and caveat context for this Boltz workflow."
      },
      {
        "name": "assembled_boltz_request",
        "label": "Assembled Boltz Request",
        "maps_to": "protease_ligand_setup.assembled_boltz_request",
        "description": "Traceable summary of the protein, ligand, MSA, and run options prepared for Boltz."
      },
      {
        "name": "affinity_summary",
        "label": "Affinity-Style Summary",
        "maps_to": "boltz_boltz2_affinity_predictor.affinity_summary",
        "description": "Parsed Boltz-2 binder probability and affinity-like outputs for this protease-ligand prediction."
      },
      {
        "name": "confidence_summary",
        "label": "Structure Confidence Summary",
        "maps_to": "boltz_boltz2_affinity_predictor.confidence_summary",
        "description": "Parsed Boltz-2 confidence outputs for the predicted protease-ligand complex."
      },
      {
        "name": "structure_artifacts",
        "label": "Predicted Complex Structure Artifacts",
        "maps_to": "boltz_boltz2_affinity_predictor.structure_artifacts",
        "description": "File-backed predicted complex structures used by the 3D visualisation."
      },
      {
        "name": "run_metadata",
        "label": "Boltz Run Metadata",
        "maps_to": "boltz_boltz2_affinity_predictor.run_metadata",
        "description": "Runtime status, command metadata, logs, and caveats for the latest Boltz invocation."
      },
      {
        "name": "prediction_evidence",
        "label": "Conservative Prediction Evidence",
        "maps_to": "protease_prediction_interpreter.prediction_evidence",
        "description": "Interpreted Boltz output evidence with request traceability and explicit scientific caveats."
      }
    ]
  },
  "tags": [
    "boltz-workflow",
    "boltz",
    "protein-ligand",
    "affinity",
    "structural-biology",
    "guided-workflow",
    "gpu",
    "antiviral",
    "protease",
    "sars-cov-2"
  ],
  "title": "Boltz Workflow: Antiviral Protease",
  "models": [
    {
      "path": "owned/models/antiviral_target_context",
      "alias": "antiviral_target_context",
      "parameters": {
        "scenario": {
          "caveat": "Boltz-2 outputs are computational structure and affinity-style predictions for hypothesis generation; they are not experimental binding, potency, selectivity, clinical, or efficacy evidence.",
          "source_pdb": "7VH8",
          "ligand_name": "Nirmatrelvir reference protease inhibitor",
          "ligand_role": "reference protease inhibitor",
          "target_name": "SARS-CoV-2 3C-like main protease",
          "disease_area": "antiviral discovery",
          "target_family": "viral 3C-like protease",
          "workflow_name": "Antiviral Protease Workflow",
          "workflow_context": "Guided Boltz-2 known-example workflow for SARS-CoV-2 3C-like main protease and Nirmatrelvir reference protease inhibitor",
          "workflow_question": "What does Boltz-2 predict for this viral protease and reference inhibitor-like ligand?",
          "source_pubchem_cid": "155903259",
          "interpretation_scope": "Learning and early hypothesis generation only",
          "protein_sequence_length": 306
        },
        "integration_step": 0.01
      },
      "provenance": {
        "owned_path": "owned/models/antiviral_target_context"
      }
    },
    {
      "path": "owned/models/protease_ligand_setup",
      "alias": "protease_ligand_setup",
      "parameters": {
        "workflow_kind": "single",
        "workflow_name": "Antiviral Protease Workflow",
        "integration_step": 0.01,
        "default_run_options": {
          "source_pdb": "7VH8",
          "ligand_name": "Nirmatrelvir reference protease inhibitor",
          "target_name": "SARS-CoV-2 3C-like main protease",
          "workflow_name": "Antiviral Protease Workflow",
          "workflow_context": "Guided Boltz-2 known-example workflow for SARS-CoV-2 3C-like main protease and Nirmatrelvir reference protease inhibitor",
          "source_pubchem_cid": "155903259",
          "interpretation_scope": "Learning and early hypothesis generation only"
        },
        "default_ligand_smiles": "CC1([C@@H]2[C@H]1[C@H](N(C2)C(=O)[C@H](C(C)(C)C)NC(=O)C(F)(F)F)C(=O)N[C@@H](C[C@@H]3CCNC3=O)C#N)C",
        "default_protein_sequence": "SGFRKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDVVYCPRHVICTSEDMLNPNYEDLLIRKSNHNFLVQAGNVQLRVIGHSMQNCVLKLKVDTANPKTPKYKFVRIQPGQTFSVLACYNGSPSGVYQCAMRPNFTIKGSFLNGSCGSVGFNIDYDCVSFCYMHHMELPTGVHAGTDLEGNFYGPFVDRQTAQAAGTDTTITVNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYEPLTQDHVDILGPLSAQTGIAVLDMCASLKELLQNGMNGRTILGSALLEDEFTPFDVVRQCSGVTFQ"
      },
      "provenance": {
        "owned_path": "owned/models/protease_ligand_setup"
      }
    },
    {
      "path": "owned/models/boltz_boltz2_affinity_predictor",
      "alias": "boltz_boltz2_affinity_predictor",
      "parameters": {
        "override": true,
        "accelerator": "gpu",
        "runtime_mode": "managed",
        "output_format": "mmcif",
        "sampling_steps": 200,
        "use_msa_server": true,
        "recycling_steps": 3,
        "diffusion_samples": 1
      },
      "provenance": {
        "owned_path": "owned/models/boltz_boltz2_affinity_predictor"
      }
    },
    {
      "path": "owned/models/protease_prediction_interpreter",
      "alias": "protease_prediction_interpreter",
      "parameters": {
        "mode": "single",
        "caveat": "Boltz-2 outputs are computational structure and affinity-style predictions for hypothesis generation; they are not experimental binding, potency, selectivity, clinical, or efficacy evidence.",
        "core_alias": "boltz_boltz2_affinity_predictor",
        "workflow_name": "Antiviral Protease Workflow",
        "integration_step": 0.01
      },
      "provenance": {
        "owned_path": "owned/models/protease_prediction_interpreter"
      }
    },
    {
      "path": "owned/models/visualisation",
      "alias": "visualisation",
      "parameters": {
        "mode": "boltz",
        "lab_title": "Boltz Workflow: Antiviral Protease",
        "source_alias": "boltz_boltz2_affinity_predictor",
        "context_alias": "antiviral_target_context",
        "assembler_alias": "protease_ligand_setup",
        "integration_step": 0.01,
        "interpreter_alias": "protease_prediction_interpreter"
      },
      "provenance": {
        "owned_path": "owned/models/visualisation"
      }
    }
  ],
  "wiring": [
    {
      "to": [
        "protease_ligand_setup.scenario_context",
        "protease_prediction_interpreter.scenario_context",
        "visualisation.antiviral_target_context_scenario_context"
      ],
      "from": "antiviral_target_context.scenario_context"
    },
    {
      "to": [
        "boltz_boltz2_affinity_predictor.protein_sequence"
      ],
      "from": "protease_ligand_setup.protein_sequence"
    },
    {
      "to": [
        "boltz_boltz2_affinity_predictor.ligand_smiles"
      ],
      "from": "protease_ligand_setup.ligand_smiles"
    },
    {
      "to": [
        "boltz_boltz2_affinity_predictor.msa_path"
      ],
      "from": "protease_ligand_setup.msa_path"
    },
    {
      "to": [
        "boltz_boltz2_affinity_predictor.run_options"
      ],
      "from": "protease_ligand_setup.run_options"
    },
    {
      "to": [
        "protease_prediction_interpreter.assembled_boltz_request",
        "visualisation.protease_ligand_setup_assembled_boltz_request"
      ],
      "from": "protease_ligand_setup.assembled_boltz_request"
    },
    {
      "to": [
        "visualisation.boltz_boltz2_affinity_predictor_affinity_summary",
        "protease_prediction_interpreter.boltz_boltz2_affinity_predictor_affinity_summary"
      ],
      "from": "boltz_boltz2_affinity_predictor.affinity_summary"
    },
    {
      "to": [
        "visualisation.boltz_boltz2_affinity_predictor_confidence_summary",
        "protease_prediction_interpreter.boltz_boltz2_affinity_predictor_confidence_summary"
      ],
      "from": "boltz_boltz2_affinity_predictor.confidence_summary"
    },
    {
      "to": [
        "visualisation.boltz_boltz2_affinity_predictor_structure_artifacts",
        "protease_prediction_interpreter.boltz_boltz2_affinity_predictor_structure_artifacts"
      ],
      "from": "boltz_boltz2_affinity_predictor.structure_artifacts"
    },
    {
      "to": [
        "visualisation.boltz_boltz2_affinity_predictor_run_metadata",
        "protease_prediction_interpreter.boltz_boltz2_affinity_predictor_run_metadata"
      ],
      "from": "boltz_boltz2_affinity_predictor.run_metadata"
    },
    {
      "to": [
        "visualisation.protease_prediction_interpreter_prediction_evidence"
      ],
      "from": "protease_prediction_interpreter.prediction_evidence"
    }
  ],
  "runtime": {
    "duration": 0.01,
    "settle_steps": 1,
    "initial_inputs": {},
    "communication_step": 0.01
  },
  "description": "Guided Boltz-2 workflow for exploring a viral 3C-like protease target with a nirmatrelvir reference ligand example, binder probability, affinity-like value, confidence metrics, and reproducible report context.",
  "schema_version": "2.0"
}

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