X Openai Boltz Small Molecule Design F03693f

---
name: x-openai-boltz-small-molecule-design-f03693f
description: Design new small-molecule binders with Boltz. Use when generating novel ligands or hits for a target without a fixed compound library. Not for screening existing molecules or one-off docking.
---

### 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 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](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` with the agent runtime's background/non-blocking command facility; it polls, paginates, downloads per-hit structures, and exits when terminal. Discover the host’s supported background or retained-process mechanism and keep its returned process handle when available; treat `download-status` plus the run directory as the durable source of truth. If a supported scheduler is available and monitoring is authorized, schedule a status check with that host’s actual API. Otherwise return the status command without claiming future monitoring. 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.
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](references/results.md) for output layout and metric details.

## Command Pattern

```bash
# Replace placeholders with concrete absolute paths before running.
# Use a short descriptive run name, for example: sm-design-<target>-<batch>-v1

boltz-api small-molecule:design estimate-cost \
  --input @yaml:///absolute/path/payload.yaml

boltz-api small-molecule:design 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 current host's documented background or retained-process mode.
# Keep its actual returned handle; do not assume a particular API or use shell detachment
# when the runner may clean up child processes.
boltz-api download-results \
  --id "<job-id-from-start>" --name "<run-name>" \
  --root-dir "/absolute/path/boltz-experiments" \
  --poll-interval-seconds 60
# -> /absolute/path/boltz-experiments/<run-name>/results/<pres_*>/...
```

Payload keys are `num_molecules`, `target`, `chemical_space`, `molecule_filters` — the API body field names.

## Always Do This

- Enforce `10 <= num_molecules <= 1,000,000` before calling `estimate-cost`. The server rejects values outside that range.
- Cost is a flat $0.025 per molecule (size-independent). `estimate-cost` returns the authoritative total.
- Treat pocket residue indices as 0-based.
- 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: for example `--target @yaml:///absolute/path/target.yaml` or `--molecule-filters @json:///absolute/path/filters.json`. Piped YAML / JSON on stdin also works, but it must use API body field names. Never use `@file://`.
- Use the same slug as both `--idempotency-key` at submit and `--name` on `download-results`.
- 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`. Use the current host’s documented process/session interface. Do not append `&` or use `nohup` when that runner may clean up shell-backgrounded descendants before `.boltz-run.json` is fully written. If no durable process facility exists, report this limitation and provide the exact resumable command.
- After the background/session starts, do not manually wait on it or run ad hoc polling loops. Wall-clock time scales roughly with `num_molecules`: under 100 often finishes in a few minutes, 100-1,000 may take several minutes to tens of minutes, and larger runs can take longer or hours depending on inputs and system load. Don't quote a fixed duration. `--poll-interval-seconds 60` is a sensible default for the downloader. `download-results` emits JSONL progress on stderr by default; add `--progress-format text --verbose` only when you explicitly want human-readable logs.
- When the host exposes a scheduler and monitoring is authorized, 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 `num_molecules`: 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. Use the host’s actual process-status action with the saved handle 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`.
- Do not invent filters; only add `molecule_filters` on user request.

## Escape Hatch

- Payload reference: <https://api.boltz.bio/docs/api/python/resources/small_molecule/subresources/design/methods/start>
- CLI flag names: `boltz-api small-molecule:design start --help`

Read [references/api.md](references/api.md) for the `target`, `chemical_space`, and `molecule_filters` shapes (filter catalog matches the screen endpoint). Read [references/results.md](references/results.md) after download when ranking generated molecules or explaining outputs.

## Outputs

Rank from `results/index.jsonl` after `download-results`; use [references/results.md](references/results.md) for local file layout and metric meanings.