boltz-small-molecule-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 small-molecule binders (no existing library).

1. Normalize the target: one or more protein sequences into target.entities, plus optional pocket_residues (0-based) and/or reference_ligands (known binders to help locate the pocket).
2. Pick num_molecules — valid range 10 to 1,000,000 (server rejects outside it). If the user says fewer than 10, explain the floor and propose 10.
3. Only add chemical_space (e.g. "enamine_real") if the user explicitly wants generation restricted to synthesizable molecules within that library.
4. Supported optional features include chemical_space and molecule_filters; only add them on explicit request. Read references/api.md for exact shapes and filter options.
5. Author the payload YAML or JSON, run estimate-cost, show the USD cost, wait for explicit confirmation. Cost is a flat $0.025 per molecule (size-independent); still quote estimated_cost_usd from the response as the authoritative total.
6. start to submit (synchronous). Capture the ID.
7. Launch download-results through the runtime's long-running or non-blocking command facility; it polls, paginates, downloads per-hit structures, 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.
8. Rank hits from <output-root>/<run-name>/results/index.jsonl by binding_confidence for hit discovery or optimization_score for lead optimization. Each generated molecule also carries a free adme block (solubility, permeability, lipophilicity) — surface it for developability triage when the user cares about ADME, or when a top hit looks risky. Read references/results.md for output layout and metric details.