| 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; also returns free Tier-1 ADME/ADMET (solubility, permeability, lipophilicity/logD) per molecule. Not for de novo molecule design, one-off docking, or ADME on bare SMILES with no target (use boltz-small-molecule-adme). |
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.
- 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.
- 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).
- Keep default server-side filtering unless the user asks for custom filters — only add
molecule_filters on explicit request.
- Author the payload YAML or JSON, run
estimate-cost, show the USD cost, wait for explicit confirmation.
start to submit (synchronous). Capture the ID.- Launch
download-results with the agent runtime's background/non-blocking command facility — it polls, paginates list-results, downloads every per-hit structure, and exits when terminal. 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 same-thread polling, but treat download-status plus the run directory as the durable source of truth. In Codex app/desktop runtimes that expose same-thread heartbeat automations, create a heartbeat that checks download-status periodically and posts a concise completion or failure update when the download reaches a terminal state. After launching the downloader, always report the job ID, run name, and output directory. Include the next check cadence if the heartbeat was created; otherwise include the download-status command.
- 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.
Command Pattern
boltz-api small-molecule:library-screen estimate-cost \
--input @yaml:///absolute/path/payload.yaml
boltz-api small-molecule:library-screen start \
--idempotency-key "<run-name>" \
--input @yaml:///absolute/path/payload.yaml \
--raw-output --transform id
boltz-api download-results \
--id "<job-id-from-start>" --name "<run-name>" \
--root-dir "/absolute/path/boltz-experiments" \
--poll-interval-seconds 30
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 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, --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 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 is fully written.
Escape Hatch
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.
