chem-similarity-search: Reusable for AI Agents | OpenAgentSkill

Overview

Find structurally similar chemical compounds using PubChem's 2D fast similarity engine via the PUG-REST API.

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Chemical Similarity Search

Goal

To programmatically find chemical analogs, alternative precursors, and structurally similar compounds for a given target molecule using PubChem's "fastsimilarity_2d" endpoint. The skill retrieves lists of similar compounds ranked by sequence alignment of their 2D molecular fingerprints, providing CIDs, molecular weights, formulas, and SMILES strings.

Instructions

1. Search by SMILES String

Search for similar compounds by providing the canonical or isomeric SMILES. Adjust the --threshold (similarity cutoff 0-100, default is 95) to widen or narrow the search radius. Higher threshold equals higher similarity. Adjust --max_records to limit the output length.

# Env: base-agent
python .agents/skills/chem-similarity-search/scripts/similarity_search.py \
  --smiles "CC(=O)Oc1ccccc1C(=O)O" \
  --threshold 95 \
  --max_records 5 \
  --outdir research/aspirin_similar \
  --output aspirin_similar.json

2. Search by PubChem CID

Search directly using an exact compound's CID. This avoids translation steps for SMILES parsing.

# Env: base-agent
python .agents/skills/chem-similarity-search/scripts/similarity_search.py \
  --cid 2244 \
  --threshold 90 \
  --max_records 10 \
  --outdir research/aspirin_similar \
  --output cid_2244_similar.json

Examples

We can test extracting highly similar analogs (Threshold 95) for Aspirin (CID: 2244 or SMILES: CC(=O)Oc1ccccc1C(=O)O).

# Env: base-agent
python .agents/skills/chem-similarity-search/scripts/similarity_search.py \
  --cid 2244 \
  --threshold 95 \
  --max_records 5 \
  --outdir .agents/skills/chem-similarity-search/examples/aspirin_analogs \
  --output aspirin_analogs.json

Constraints

Rate Limiting: PubChem PUG REST API enforces per-user throttling limits. Heavy bursts will result in HTTP 503 Server Busy errors. The script implements an exponential backoff retry mechanism.
2D Similarity: Uses exact structural bit-vector fingerprints. Stereochemical and 3D properties do not strongly affect the score.
Network: Internet access is required.

Author: Bowen Deng Contact: GitHub @learningmatter-mit

View source ↗

File metadata

name: chem-similarity-search
description: Find structurally similar chemical compounds using PubChem's 2D fast similarity engine via the PUG-REST API.
category: [chemistry, drug-discovery]

View original text

---
name: chem-similarity-search
description: Find structurally similar chemical compounds using PubChem's 2D fast similarity engine via the PUG-REST API.
category: [chemistry, drug-discovery]
---

# Chemical Similarity Search

## Goal
To programmatically find chemical analogs, alternative precursors, and structurally similar compounds for a given target molecule using PubChem's "fastsimilarity_2d" endpoint. The skill retrieves lists of similar compounds ranked by sequence alignment of their 2D molecular fingerprints, providing CIDs, molecular weights, formulas, and SMILES strings.

## Instructions

### 1. Search by SMILES String
Search for similar compounds by providing the canonical or isomeric SMILES.
Adjust the `--threshold` (similarity cutoff 0-100, default is 95) to widen or narrow the search radius. Higher threshold equals higher similarity.
Adjust `--max_records` to limit the output length.

```bash
# Env: base-agent
python .agents/skills/chem-similarity-search/scripts/similarity_search.py \
  --smiles "CC(=O)Oc1ccccc1C(=O)O" \
  --threshold 95 \
  --max_records 5 \
  --outdir research/aspirin_similar \
  --output aspirin_similar.json
```

### 2. Search by PubChem CID
Search directly using an exact compound's CID. This avoids translation steps for SMILES parsing.

```bash
# Env: base-agent
python .agents/skills/chem-similarity-search/scripts/similarity_search.py \
  --cid 2244 \
  --threshold 90 \
  --max_records 10 \
  --outdir research/aspirin_similar \
  --output cid_2244_similar.json
```

## Examples

We can test extracting highly similar analogs (Threshold 95) for Aspirin (CID: 2244 or SMILES: `CC(=O)Oc1ccccc1C(=O)O`).

```bash
# Env: base-agent
python .agents/skills/chem-similarity-search/scripts/similarity_search.py \
  --cid 2244 \
  --threshold 95 \
  --max_records 5 \
  --outdir .agents/skills/chem-similarity-search/examples/aspirin_analogs \
  --output aspirin_analogs.json
```

## Constraints
- **Rate Limiting**: PubChem PUG REST API enforces per-user throttling limits. Heavy bursts will result in `HTTP 503 Server Busy` errors. The script implements an exponential backoff retry mechanism.
- **2D Similarity**: Uses exact structural bit-vector fingerprints. Stereochemical and 3D properties do not strongly affect the score.
- **Network**: Internet access is required.

---
---

**Author:** Bowen Deng
**Contact:** [GitHub @learningmatter-mit](https://github.com/learningmatter-mit)

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Review before install: Avoid automatic install

License: MIT

Dependency or permission surface needs review
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The SKILL.md excerpt shows an incomplete line in the script (e.g., 'elif' with no following code), but this is likely due to truncation in the provided excerpt and not a real issue.
Quality score needs review
Permission surface needs review: secrets or environment access, shell or command execution
Stars/forks activity: 161 stars, 24 forks; issue activity unavailable in current metadata
Dependency/runtime risk: command execution surface, credential or environment access
Permission surface: secrets or environment access, shell or command execution

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Source & usage notes

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Repository metadata and review signals are advisory. Popularity, source discovery and successful execution are different facts.

Source repository: learningmatter-mit/AtomisticSkills
License: MIT
Version: 1.0.0
Last GitHub push: Sep 3, 2026
Registry updated: Sep 6, 2026
Instruction path: .agents/skills/chem-similarity-search/SKILL.md @ d1f7ecfda2cd

Version reported in registry metadata; check source releases before relying on it.

Quality

69/100

Promising

Trust

62/100

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