boltz-small-molecule-screen

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 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 help locate the pocket).
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, run estimate-cost, show the USD cost, wait for explicit confirmation.
5. start to submit (synchronous). Capture the ID.
6. Launch download-results through the runtime's long-running or non-blocking command facility — it polls, paginates list-results, downloads every per-hit structure, and exits when terminal. Use the mechanism the runtime documents; consult boltz-cli-setup if unsure. After launching the downloader, always report the job ID, run name, and output directory. If the runtime can schedule follow-up checks, schedule a download-status check and state the cadence; 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. Each result also carries a free adme block (solubility, permeability, lipophilicity) — include it for developability triage when the user cares about ADME, or when a top hit looks risky. Read references/results.md for output layout, metrics, ADME, and filtered-input accounting.