boltz small molecule screen

Workflow

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 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.
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 [blocked] for output layout, metrics, ADME, 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 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

# 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 30
# -> /absolute/path/boltz-experiments/<run-name>/results/<pres_*>/...

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 .boltz-run.json is fully written.
• After the background/session starts, do not manually wait on it or run ad hoc polling loops. download-results emits JSONL progress on stderr by default; add --progress-format text --verbose only when you explicitly want human-readable logs.
• In Codex app/desktop runtimes with same-thread heartbeat automation support, schedule a heartbeat after launching download-results. The heartbeat should run boltz-api --format json download-status --name "<run-name>" --root-dir "/absolute/path/boltz-experiments" and stop once terminal. Choose cadence by molecule count: under 100 -> every 1-2 minutes; 100-1,000 -> every 5 minutes; over 1,000 -> every 15 minutes. Post only material status changes or terminal completion/failure. Poll the saved session_id with an empty write_stdin only for interactive, user-requested progress checks. Never run a manual poll loop in the current turn.
• If the current host has no heartbeat automation support, do not claim an automatic next check. Report the job ID, run name, output directory, and the command needed to check download-status.
• If detached download needs to be restarted, re-run boltz-api download-results with the same --name "<run-name>" and the same --root-dir.
• Cost is a flat $0.025 per molecule (size-independent). estimate-cost returns the authoritative total — always use it.
• Poll interval: --poll-interval-seconds 30 is a reasonable downloader default. Wall-clock time scales roughly with the number of molecules: 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. Don't quote a fixed duration, and 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

Outputs