Zero-Shot Mutation Workflow
Overview
Orchestrates VenusFactory mutation tools: sequence-only PLMs (ESM-1v / ESM2 / VenusPLM) or structure-aware PLMs (ESM-IF1 / SaProt / ProtSSN / MIF-ST). Outputs CSV + heatmap paths in the rich JSON envelope — treat scores as computational hypotheses, not wet-lab results.
VenusFactory execution
read_skillwithskill_id: zero_shot_mutation_workflow(this file).- Call the hub tools below by exact name (do not invent Forge/ESM SDK calls).
- Parse
status,file_info.file_path, and anydata/ heatmap paths.
Project Tools (VenusFactory2)
| Tool | Args | Returns | When |
|---|---|---|---|
| zero_shot_mutation_sequence_prediction | sequence or fasta_file; model_name (default ESM2-650M); backend (local/pjlab); optional out_dir |
status JSON + CSV/heatmap | Only sequence available |
| zero_shot_mutation_structure_prediction | structure_file (PDB); model_name (default ESM-IF1); backend; optional out_dir |
status JSON + CSV/heatmap | PDB available (prefer over sequence-only) |
| read_fasta | file_path |
sequence content | Inspect uploaded FASTA |
| get_seq_from_pdb_chain_a | pdb_file |
chain A sequence | Need sequence from structure |
| render_protein_structure | pdb_path, out_dir, style options |
image under file_info |
Visualize top mutation sites |
Sequence models: ESM-1v, ESM2-650M, ESM-1b, VenusPLM.
Structure models: ESM-IF1, SaProt, ProtSSN, MIF-ST (and related names exposed by the tool).
Workflow
A. Sequence-only path
- Ensure FASTA via
read_fastaor passsequencedirectly. - Call
zero_shot_mutation_sequence_predictionwith an explicitout_dirunder the session workspace. - Summarize top-ranked substitutions; warn that scores are model-dependent.
B. Structure path (preferred when PDB exists)
- Validate PDB path (may come from
predict_structure_esmfoldordownload_alphafold_structure_by_uniprot_id). - Call
zero_shot_mutation_structure_prediction. - Optional:
render_protein_structurehighlighting candidate sites; optional cross-check withpredict_residue_function(Activity/Binding/Conserved Site).
When NOT to use
- Designing a new sequence for a fixed backbone →
proteinmpnn_design_workflow - Need experimental structure QA / AlphaFold confidence →
alphafold_database/protein_structure_pipeline - Homolog discovery →
protein_sequence_similarity_searchorfoldseek_structural_similarity
Common mistakes
- Calling non-existent ESM Forge APIs instead of hub tools.
- Using structure models without a real PDB path.
- Presenting zero-shot ranks as measured ΔΔG / activity without caveats.
- Omitting
out_dirwhen the session needs a stable artifact path.