boltz-small-molecule-screen

name	boltz-small-molecule-screen
description	Screen existing small-molecule libraries with Boltz. Use when docking, scoring, or ranking a supplied SMILES or compound library against a target. Not for de novo molecule design or one-off docking.

Workflow

If boltz-api reports missing or expired authentication, surface the error to the user. Do not attempt to re-authenticate; the host environment must provide BOLTZ_API_KEY.

Use this skill when the user already has candidate molecules.

1. Normalize the library from raw SMILES, a CSV (auto-detect the SMILES column), .smi, or .txt into the molecules list. Each entry is {smiles, id?}; the optional id is echoed back as external_id on each result.
2. Normalize the target: one or more protein sequences into target.entities, plus optional pocket_residues (0-based) and/or reference_ligands (SMILES of known binders to seed pocket detection).
3. Keep default server-side filtering unless the user asks for custom filters — only add molecule_filters on explicit request.
4. Author the payload YAML or JSON.
5. start to submit (synchronous). Capture the ID.
6. Launch download-results as a long-running/background command in whatever mode the host agent harness provides — it polls, paginates list-results, downloads every per-hit structure, and exits when terminal. After launching it, schedule the host's available follow-up/notification mechanism, if one exists, to check download-status periodically and notify the user when the download reaches a terminal state. Always report the job ID, run name, and output directory. Include the next check cadence if a follow-up was scheduled; otherwise include the download-status command.
7. When done, rank from <output-root>/<run-name>/results/index.jsonl. Sort by binding_confidence for hit discovery or optimization_score for lead optimization; these are parallel intents, not a fallback hierarchy. Report the top 5-10 hits with smiles, the chosen ranking metric, key confidence metrics, and structure path. Read references/results.md for output layout, metrics, and filtered-input accounting.

Command Pattern

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

boltz-api small-molecule:library-screen 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 as a
# long-running/background command via the host agent harness.
boltz-api download-results \
  --id "<job-id-from-start>" --name "<run-name>" \
  --root-dir "/absolute/path/boltz-experiments" \
  --poll-interval-seconds 30
# -> /absolute/path/boltz-experiments/<run-name>/results/<pres_*>/...

Payload keys are molecules, target, molecule_filters — the API body field names, not the direct CLI flag names --molecule / --target / --molecule-filters.

Always Do This

• 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. 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, --molecule-filters @json:///absolute/path/filters.json, or repeated --molecule @json:///absolute/path/mol-1.json entries. Piped YAML / JSON on stdin also works, but it must use API body field names. Never use @file:// or @./.
• Treat pocket residue indices as 0-based.
• Do not invent medicinal-chemistry filters. Only add molecule_filters if the user asks; mention the catalog as an option.
• Use the same slug as both --idempotency-key at submit and --name on download-results so re-runs resume via .boltz-run.json.
• In permission-gated agents, 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.
• Run download-results through the host harness's long-running/background command facility. After it starts, do not manually wait on it or run ad hoc polling loops. If the host harness provides a managed follow-up/notification mechanism, schedule it to check download-status, notify the user on terminal completion/failure, and stop once terminal. If not, do not claim an automatic next check.
• download-results emits JSONL progress on stderr by default; add --progress-format text --verbose only when you explicitly want human-readable logs.
• Prefer boltz-api --format json download-status --name "<run-name>" --root-dir "/absolute/path/boltz-experiments" for structured local checkpoint state. When the host provides a managed follow-up mechanism, use it for automatic checks with cadence based on molecule count: under 100 -> every 1-2 minutes; 100-1,000 -> every 5 minutes; over 1,000 -> every 15 minutes. Never run a manual poll loop in the current turn.
• If a detached download needs to be restarted, re-run boltz-api download-results with the same --name "<run-name>" and the same --root-dir.
• Poll interval: --poll-interval-seconds 30 is a reasonable downloader default. Wall-clock time scales roughly with library size: under 100 often finishes in a few minutes, 100-1,000 may take several minutes to tens of minutes, and larger screens can take longer or hours depending on inputs and system load. Never tell the user a 10-candidate screen will take 30 minutes or hours.

Escape Hatch

• Payload reference: https://api.boltz.bio/docs/api/python/resources/small_molecule/subresources/library_screen/methods/start
• CLI flag names: boltz-api small-molecule:library-screen start --help

Read references/api.md for the molecules, target, and molecule_filters shapes, including the built-in SMARTS filters and RDKit descriptor ranges. Read references/results.md after download when ranking hits or explaining missing/filtered inputs.

Outputs

Rank from results/index.jsonl after download-results; use references/results.md for the local file layout, metric meanings, and filtered-input accounting.