boltz-protein-design

Workflow

If boltz-api is missing from PATH, use boltz-cli-setup for install/update guidance before retrying. If a command reports missing or expired authentication, use boltz-cli-setup to start boltz-api auth login --device-code before retrying; do not ask permission first. If the agent host sandbox blocks boltz-api install/auth/API calls, use boltz-cli-setup to request the host sandbox bypass/escalation needed for user-wide CLI install, browser login, credential storage, temp files, or API access before retrying.

Use this skill when the user wants de novo protein / peptide / antibody / nanobody binders.

1. Normalize the target (same shape as protein-screen): structure_template if a CIF/PDB is available, else no_template.
2. Pick the binder_specification variant. Supported variants include:
   • boltz_curated — recommended default for antibody and nanobody design. Boltz selects from maintained scaffold/template lists (binder: boltz_antibody or boltz_nanobody).
   • structure_template — redesign motifs in an existing binder scaffold (CIF + design_motifs with replacement / insertion segments).
   • no_template — generate from the sequence DSL (fixed residues + designed segments like 5..10 or 8).
3. For antibody or nanobody requests, ask before authoring the payload: "I recommend Boltz's curated antibody/nanobody scaffolds for this. Do you want the curated default, or do you have custom scaffold structures/CDR motifs to use?" If the user picks curated, use type: boltz_curated; if they want custom scaffold control, use type: structure_template.
4. Pick modality: peptide, antibody, nanobody, or custom_protein for structure_template and no_template. Do not include modality on boltz_curated; use binder instead.
5. Pick num_proteins — minimum 10, server rejects lower. If the user says a smaller number, explain the floor and propose 10.
6. Supported optional features include rules such as excluded amino acids, excluded sequence motifs with X wildcards, and max hydrophobic fraction. Add rules only on request; read references/api.md for exact shapes and examples.
7. Author the payload YAML or JSON, run estimate-cost, show the USD cost, wait for explicit confirmation. Cost scales with total complex length (target + binder), not just num_proteins. A small peptide + small target runs ≈$0.025 per design; larger complexes (e.g. GFP + 20-mer binder) run ≈$0.05 per design. Always quote the exact figure from estimate-cost.
8. start to submit. Capture the ID.
9. Launch download-results with the agent runtime's background/non-blocking command facility. In Claude Code, use Bash with run_in_background: true. In Codex, run download-results as a foreground shell command with yield_time_ms: 1000; if Codex returns a session_id, keep it for optional later polling. After launching it, report the job ID, run name, and output directory, then end the turn immediately. Do not wait on the background session unless the user explicitly asks for progress.
10. Rank from <output-root>/<run-name>/results/index.jsonl by binding_confidence descending. Use iptm and min_interaction_pae as tiebreakers. optimization_score is not emitted for this endpoint. Read references/results.md for output layout and metric details.

Command Pattern

# Replace placeholders with concrete absolute paths before running.
# Use a short descriptive run name, for example: protein-design-<modality>-<target>-v1

boltz-api protein:design estimate-cost \
  --input @yaml:///absolute/path/payload.yaml

boltz-api protein:design start \
       --idempotency-key "<run-name>" \
       --input @yaml:///absolute/path/payload.yaml \
       --raw-output --transform id

# Copy the printed job ID into this command, then launch it in the agent
# runtime's background/non-blocking mode.
# Claude Code: Bash with run_in_background=true.
# Codex: foreground shell command with yield_time_ms=1000; keep the returned session_id if one is provided.
# Do not append "&" or use nohup in Codex.
boltz-api download-results \
  --id "<job-id-from-start>" --name "<run-name>" \
  --root-dir "/absolute/path/boltz-experiments" \
  --poll-interval-seconds 60

Payload keys are num_proteins, target, binder_specification — API body field names.

Always Do This

• Enforce num_proteins >= 10 before calling estimate-cost. Server rejects anything lower.
• Cost scales with total complex length (target + binder). Always quote estimated_cost_usd from estimate-cost.
• For antibody or nanobody design, recommend binder_specification.type: boltz_curated and ask the user to confirm they do not want custom scaffold/CDR control before building the payload. Use binder: boltz_antibody for antibody/Fab requests and binder: boltz_nanobody for nanobody/VHH requests.
• Residue indices are 0-based everywhere (design_motifs.start_index/end_index, after_residue_index, epitope_residues, flexible_residues, bonds, constraints).
• For CIF/PDB bytes, use @data:///abs/path/file.cif inside structure.data. Don't use bare @path.
• Sequence DSL for designed_protein.value: uppercase letters = fixed residues; integer N = exactly N designed residues; MIN..MAX = variable-length designed segment. Examples: "20", "5..10", "ACDE8GHI", "MKTAYI5..10VKSHFSRQ".
• Keep payload field names exactly as the API body names shown in references/api.md.
• Use absolute paths for the output root, payload files, and embedded target files. Do not cd into the run directory for follow-up commands; pass the same --root-dir and use absolute paths so later relative paths do not drift.
• Prefer one merged top-level payload via --input @yaml:///absolute/path/payload.yaml or @json:///absolute/path/payload.json for estimate-cost and start. Keep --idempotency-key and --workspace-id top-level; if they also appear inside --input, the top-level flags win.
• Direct object flags still work as overrides, such as --target @yaml:///absolute/path/target.yaml or --binder-specification @json:///absolute/path/binder.json. Piped YAML / JSON on stdin also works, but it must use API body field names. Use the same slug for both --idempotency-key and --name.
• In permission-gated agents such as Claude Code, keep each Boltz call as a top-level command that starts with boltz-api. Prefer concrete arguments over sh -c, inline environment assignments, aliases, wrapper scripts, loops, or pipelines around the boltz-api invocation unless the user already allowed that exact command form. Use --raw-output --transform id, read the printed ID, then paste that literal ID into the next download-results command.
• Prefer the agent runtime's background/non-blocking command mode for download-results. In Codex specifically, keep download-results in the foreground and set the shell tool yield to 1000 ms; Codex will return a session_id if the command is still running. Do not append & or use nohup in Codex because the tool runner may clean up shell-backgrounded descendants before .boltz-run.json is fully written.
• After the background/session starts, do not wait on it or poll it. Design jobs can take 30 min to several hours — --poll-interval-seconds 60 is a sensible default. download-results emits JSONL progress on stderr by default; add --progress-format text --verbose only when you explicitly want human-readable logs. Report the job ID, run name, output directory, and that the runtime should notify when the background command completes.
• Only check status when the user asks. In Codex, poll the saved session with an empty write_stdin, or prefer boltz-api --format json download-status --name "<run-name>" --root-dir "/absolute/path/boltz-experiments" for structured local checkpoint state. Never run a manual poll loop.
• If detached download needs to be restarted, re-run boltz-api download-results with the same --name "<run-name>" and the same --root-dir.
• Only add rules on explicit user request.

Escape Hatch

• Payload reference: https://api.boltz.bio/docs/api/resources/protein/subresources/design/methods/start/
• CLI flag names: boltz-api protein:design start --help

Read references/api.md for all binder_specification variants, motif shapes, sequence DSL, rules, modalities, and target variants. Read references/results.md after download when ranking designed binders or explaining outputs.

Outputs

Rank from results/index.jsonl after download-results; use references/results.md for local file layout, metric meanings, and the designed-binder entity type gotcha.