Rdkit

RDKit Cheminformatics Toolkit

Overview

RDKit is a comprehensive cheminformatics library providing Python APIs for molecular analysis and manipulation. This skill provides guidance for reading/writing molecular structures, calculating descriptors, fingerprinting, substructure searching, chemical reactions, 2D/3D coordinate generation, and molecular visualization. Use this skill for drug discovery, computational chemistry, and cheminformatics research tasks.

Checked against: RDKit 2026.03.5 (rdkit 2026.3.5 on PyPI, released 2026-08-03), August 2026. Official installation docs continue to recommend conda-forge for most users, while cross-platform PyPI wheels are published under the rdkit package name. rdkit-pypi is the old PyPI package name and should only appear when maintaining legacy environments.

Installation and Setup

Use uv when installing into an existing Python environment:

uv pip install rdkit

For reproducible chemistry environments, especially when mixing compiled scientific packages, conda-forge remains the upstream recommendation:

conda create -c conda-forge -n my-rdkit-env rdkit
conda activate my-rdkit-env

Avoid installing both conda rdkit and PyPI rdkit/rdkit-pypi into the same environment unless you are deliberately debugging packaging behavior. Mixed installs can make it unclear which binary extension is being imported.

Core Capabilities

Twelve capability areas, each with worked code, are documented in [references/corecapabilities.md](references/corecapabilities.md):

| # | Area | Covers | | --- | --- | --- | | 1 | Molecular I/O and creation | SMILES, MOL files and blocks, InChI, SDF and SMILES suppliers, multithreaded reading, writers | | 2 | Sanitization and validation | disabling automatic sanitization, manual and partial sanitization, detecting problems first | | 3 | Analysis and properties | atom and bond iteration, ring information and SSSR, chirality and stereochemistry, fragments | | 4 | Descriptors | MW, LogP, TPSA, H-bond donors/acceptors, rotatable bonds, aromatic rings, bulk calculation, drug-likeness | | 5 | Fingerprints and similarity | topological, Morgan/ECFP via rdFingerprintGenerator, MACCS, atom pair, torsion, Avalon; Tanimoto and other metrics; Butina clustering | | 6 | Substructure searching | SMARTS queries, match retrieval, and a library of common patterns | | 7 | Chemical reactions | reaction SMARTS, applying reactions, reaction fingerprints | | 8 | 2D and 3D coordinates | depiction, template alignment, ETKDG embedding, force-field optimization, RMSD, constrained embedding | | 9 | Visualization | single and grid images, substructure highlighting, custom drawer options, Jupyter integration, fingerprint bit environments | | 10 | Molecular modification | explicit hydrogens, Kekulization, aromaticity, substructure replacement, charge neutralization | | 11 | Hashes and standardization | Murcko scaffold and canonical hashes, regioisomer hashes, randomized SMILES for augmentation | | 12 | Pharmacophore and 3D features | feature factories and feature extraction |

Worked workflows and the performance, thread-safety, and version-sensitivity notes are in [references/workflowsandbestpractices.md](references/workflowsandbestpractices.md).

Prefer portable exchange formats (SMILES, SDF) for shared data; for local caches RDKit's binary molecule representation avoids generic pickle.

Common Pitfalls

1. Forgetting to check for None: Always validate molecules after parsing
2. Sanitization failures: Use DetectChemistryProblems() to debug
3. Missing hydrogens: Use AddHs() when calculating properties that depend on hydrogen
4. 2D vs 3D: Generate appropriate coordinates before visualization or 3D analysis
5. SMARTS matching rules: Remember that unspecified properties match anything
6. Thread safety with MolSuppliers: Don't share supplier objects across threads

Resources

references/

All five bundled reference documents, loaded only when needed:

• [references/corecapabilities.md](references/corecapabilities.md) - the twelve capability areas above, each with worked code
• [references/workflowsandbestpractices.md](references/workflowsandbestpractices.md) - end-to-end workflows plus performance, thread-safety, and version-sensitivity notes
• [references/apireference.md](references/apireference.md) - RDKit modules, functions, and classes organized by functionality
• [references/descriptorsreference.md](references/descriptorsreference.md) - the available molecular descriptors with descriptions
• [references/smartspatterns.md](references/smartspatterns.md) - SMARTS patterns for functional groups and structural features

Only the files listed in references/ and scripts/ are bundled local resources. Names such as rdkit, datamol, scipy, and sklearn refer to installable Python packages, not local files in this skill.

scripts/

# Descriptors for one molecule, or a whole file to CSV
python skills/rdkit/scripts/molecular_properties.py "CC(=O)Oc1ccccc1C(=O)O"
python skills/rdkit/scripts/molecular_properties.py --file library.smi --output properties.csv

# Fingerprint similarity screen; --method morgan|rdkit|maccs|atompair|torsion
python skills/rdkit/scripts/similarity_search.py "c1ccccc1O" library.sdf --threshold 0.6

# SMARTS filtering, with predefined libraries via --list-patterns
python skills/rdkit/scripts/substructure_filter.py library.smi --pattern "C(=O)[OH]" --report hits.csv

Each exits nonzero and writes to stderr on failure, so they compose in a pipeline. They are equally usable as templates for custom workflows.

Composing with the rest of the bundle

• datamol → instead: the same standardization, clustering and parallel work with sensible

defaults. Reach for rdkit only when you need control datamol does not expose.

• medchem → after: real triage. Its rule catalogue and the full PAINS/NIBR alert sets are what you

want for library filtering; substructure_filter.py here is a general SMARTS tool, not a curated alert set.

• molfeat → after: turning molecules into model-ready features rather than hand-rolled fingerprints.
• chembl → before: measured bioactivity to featurize, rather than a library you invented.
• chemical-space → after: once a SMARTS query defines the chemotype, find purchasable examples.
• admet-prediction / deepchem / pytdc → after: descriptors and fingerprints from here are the

input those models expect. Desalt and standardise first or you predict on the wrong species.

Source & license

This open-source skill is cataloged on AgentStack and links to its original source — we do not rehost the code.

• Author: K-Dense-AI
• Source: K-Dense-AI/drug-discovery-agent-skills
• License: MIT
• Homepage: www.k-dense.ai

Install and usage instructions live in the source repository linked above.