X Openai Boltz Small Molecule Screen C199e4f

---
name: x-openai-boltz-small-molecule-screen-c199e4f
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).
---

### 导出副本边界与技能别名

迁移、安装、修复和经验回写只作用于当前加载的目标宿主技能副本。原 Codex 技能/MCP、下载的源码和 `original-skills` 均为来源材料，不因执行本副本而写入；只有用户另行明确要求配置 Codex 产品本身时，才按该产品流程处理指定目标。脚本需要安装目录或状态目录时，显式提供目标路径；不得从 `CODEX_HOME` 隐式推断写入位置。

跨技能名称可能沿用源库别名。先查 [技能别名表](../../skill-aliases.json)，优先选择同来源、同插件的条目，再使用其 `id` 调用或读取对应入口；不得假定旧 `$skill`、`superpowers:skill` 名称在新宿主直接注册。不能确定目标时先核对，不替换真实产品命令或 Shell 环境变量。

## 跨宿主使用约定

本副本供支持 Agent Skills 的客户端使用。先检查当前宿主实际提供的工具、权限和已连接服务，再执行正文工作流。原文中的宿主工具标识是能力参考；只有实际发现该工具时才可调用，其他宿主应使用经核验的等价 MCP、CLI 或 API。没有等价能力的步骤必须报告不可用，不能虚构调用或完成状态。

技能资源以本技能目录为基准；输出写入当前项目中用户指定的位置。通过技能名称或自然语言触发，具体快捷命令由宿主决定。涉及真实产品、模型 API、协议字段和官方网址的名称保持原意。授权、审批、隐私和工具范围限制在迁移后仍然有效；不得为兼容而扩大权限。具体依赖与迁移说明见同目录 `PORTABILITY.md`。

## 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` with the agent runtime's background/non-blocking command facility — it polls, paginates `list-results`, downloads every per-hit structure, and exits when terminal. Discover the host's supported long-running command mechanism and retain its returned session handle, if any. If the host reaps detached child processes, keep the command in a persistent terminal or a host-managed foreground session. Treat `download-status` plus the run directory as the durable source of truth. If the host provides an authorized same-conversation scheduling capability, use it to check `download-status` periodically and report completion or failure; otherwise provide the check command without promising future execution. 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](references/results.md) for output layout, metrics, ADME, and filtered-input accounting.

## Command Pattern

```bash
# 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.
# Use the host-documented persistent command/session mechanism.
# Retain its session handle when provided.
# Do not use shell detachment when the host may reap child processes.
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_*>/...
```

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`. For a host that reaps detached descendants, keep `download-results` in a persistent foreground session and use only that host's documented non-blocking return option. Keep any returned session handle. Do not append `&` or use `nohup` unless the process lifetime is supported; otherwise the runner may stop the downloader 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.
- When the current host exposes an authorized same-conversation scheduler, schedule a status check 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. Inspect the saved command session through the host's documented status facility 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`

Read [references/api.md](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](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](references/results.md) for the local file layout, metric meanings, and filtered-input accounting.