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 for standalone ADME triage on SMILES the user already has. No protein target is involved. If the user is also screening or docking those molecules against a target, prefer boltz-small-molecule-screen — it returns the same ADME block free as part of the screen.

1. Normalize the molecules 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 so you can map results to inputs.
2. Hard cap: 128 molecules per request. If the list exceeds 128, split into batches of ≤128 and submit one request per batch (suffix the run name, for example -b1, -b2), then merge results. Never send more than 128 in one call — the API rejects it with VALIDATION_ERROR: input.molecules must contain at most 128 items.
3. Author the payload YAML or JSON, run estimate-cost, show the USD cost, wait for explicit confirmation. ADME is priced at $0.01 per molecule (size-independent); estimate-cost returns the authoritative total — always quote it.
4. run to submit and wait — ADME finishes in seconds, so it is synchronous and needs no background polling. run persists results locally under --root-dir/<run-name>/.
5. Report from <output-root>/<run-name>/run.json → output.molecules[]. For each molecule show external_id (or smiles), solubility, permeability, and lipophilicity. The three values live under each molecule's adme object. Call out any molecule with status: failed and its error (an object {code, message}, e.g. code adme_enumeration_failed, message Invalid SMILES) — adme is null there; one bad SMILES fails only that molecule, not the batch. Read references/results.md for the output layout and references/api.md for the payload and batching details.

ADME values are approximate estimates for triage and ranking, not absolute measurements.

Command Pattern

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

boltz-api predictions:adme estimate-cost \
  --model adme-v1 --input @yaml:///absolute/path/payload.yaml

# `run` is synchronous (submit + wait + persist) and finishes in seconds — run it as a
# normal foreground command. If the runtime returns a session handle because the
# command is still running, poll that handle. Do not detach it with "&" or nohup.
boltz-api predictions:adme run \
  --model adme-v1 \
  --idempotency-key "<run-name>" \
  --input @yaml:///absolute/path/payload.yaml \
  --name "<run-name>" \
  --root-dir "/absolute/path/boltz-experiments" \
  --poll-interval-seconds 5
# -> /absolute/path/boltz-experiments/<run-name>/run.json  (output.molecules[].adme)

Payload is just a molecules list — the API body field name, not the direct CLI flag. --model adme-v1 is required.

Always Do This

• Keep payload field names exactly as the API body names shown in references/api.md (molecules, each {smiles, id?}).
• Pass --model adme-v1 on every estimate-cost, run, and start.
• Enforce the 128-molecule-per-request cap. Chunk larger libraries into ≤128 batches and submit each as its own run; merge the per-batch run.json outputs when reporting.
• Use absolute paths for the output root and payload files. Do not cd into the run directory; 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 --model, --idempotency-key, and --workspace-id top-level. Never use @file:// or @./.
• Run estimate-cost and show the USD total before submitting. ADME is $0.01/molecule (size-independent); estimate-cost returns the authoritative total — always use it.
• Use the same slug as both --idempotency-key and --name so re-runs resume via .boltz-run.json.
• In permission-gated runtimes, 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 unless the user already allowed that exact command form.
• ADME run is synchronous and finishes in seconds, so unlike the screen/design endpoints it needs no long-running or non-blocking mode. Run it as a normal foreground command. If the runtime returns a session handle because the command is still running, poll that handle. Do not detach it with & or nohup.
• Do not require or accept a protein target — ADME is structure-free. If the user wants ADME and binding against a target, redirect to boltz-small-molecule-screen.

Escape Hatch

• Payload reference: https://api.boltz.bio/docs/api/resources/predictions/subresources/adme/methods/start/
• Guide: https://api.boltz.bio/docs/guides/small-molecule-adme/
• CLI flag names: boltz-api predictions:adme run --help

Read references/api.md for the molecules payload shape, the per-molecule output fields, the 128-molecule cap, and error handling.

Outputs

Read <output-root>/<run-name>/run.json and report output.molecules[]. There are no structure files — ADME returns scalar/categorical values only. Read references/results.md for the local layout and per-molecule output fields; references/api.md has the full request/response schema.