An overview of the RDKit — The RDKit 2017.09.1 documentation

# An overview of the RDKit

## What is it?

### Open source toolkit for cheminformatics

- Business-friendly BSD license
- Core data structures and algorithms in C++
- Python (2.x and 3.x) wrapper generated using Boost.Python
- Java and C# wrappers generated with SWIG
- 2D and 3D molecular operations
- Descriptor generation for machine learning
- Molecular database cartridge for PostgreSQL
- Cheminformatics nodes for KNIME (distributed from the KNIME community site: http://tech.knime.org/community/rdkit)

### Operational:

- http://www.rdkit.org
- Supports Mac/Windows/Linux
- Releases every 6 months
- Web presence:
  - Homepage: http://www.rdkit.org Documentation, links
  - Github (https://github.com/rdkit) Downloads, bug tracker, git repository
  - Sourceforge (http://sourceforge.net/projects/rdkit) Mailing lists
  - Blog (https://rdkit.blogspot.com) Tips, tricks, random stuff
  - Tutorials (https://github.com/rdkit/rdkit-tutorials) Jupyter-based tutorials for using the RDKit
  - KNIME integration (https://github.com/rdkit/knime-rdkit) RDKit nodes for KNIME
- Mailing lists at https://sourceforge.net/p/rdkit/mailman/, searchable archives available for rdkit-discuss and rdkit-devel
- Social media:
  - Twitter: @RDKit_org
  - LinkedIn: https://www.linkedin.com/groups/8192558
  - Google+: https://plus.google.com/u/0/116996224395614252219
  - Slack: https://rdkit.slack.com (invite required, contact Greg)

### History:

- 2000-2006: Developed and used at Rational Discovery for building predictive models for ADME, Tox, biological activity
- June 2006: Open-source (BSD license) release of software, Rational Discovery shuts down
- to present: Open-source development continues, use within Novartis, contributions from Novartis back to open-source version

## Functionality overview

## Basics

- Input/Output: SMILES/SMARTS, SDF, TDT, SLN 1, Corina mol2 1, PDB, sequence notation, FASTA (peptides only), HELM (peptides only)
- Substructure searching
- Canonical SMILES
- Chirality support (i.e. R/S or E/Z labeling)
- Chemical transformations (e.g. remove matching substructures)
- Chemical reactions
- Molecular serialization (e.g. mol <-> text)
- 2D depiction, including constrained depiction
- Fingerprinting: Daylight-like, atom pairs, topological torsions, Morgan algorithm, “MACCS keys”, extended reduced graphs, etc.
- Similarity/diversity picking
- Gasteiger-Marsili charges
- Bemis and Murcko scaffold determination
- Salt stripping
- Functional-group filters

### 2D

- 2D pharmacophores 1
- Hierarchical subgraph/fragment analysis
- RECAP and BRICS implementations
- Multi-molecule maximum common substructure 2
- Enumeration of molecular resonance structures
- Molecular descriptor library:
  - Topological (κ3, Balaban J, etc.)
  - Compositional (Number of Rings, Number of Aromatic Heterocycles, etc.)
  - Electrotopological state (Estate)
  - clogP, MR (Wildman and Crippen approach)
  - “MOE like” VSA descriptors
  - MQN 6
- Similarity Maps 7
- Machine Learning:
  - Clustering (hierarchical, Butina)
  - Information theory (Shannon entropy, information gain, etc.)
- Tight integration with the Jupyter notebook (formerly the IPython notebook) and Pandas.

### 3D

- 2D->3D conversion/conformational analysis via distance geometry, including optional use of experimental torsion angle potentials 9
- UFF and MMFF94/MMFF94S implementations for cleaning up structures
- Pharmacophore embedding (generate a pose of a molecule that matches a 3D pharmacophore) 1
- Feature maps
- Shape-based similarity
- RMSD-based molecule-molecule alignment
- Shape-based alignment (subshape alignment 3) 1
- Unsupervised molecule-molecule alignment using the Open3DAlign algorithm 4
- Integration with PyMOL for 3D visualization
- Molecular descriptor library:
  - Moments-of-inertia based descriptors: PMI, NPR, PBF, etc.
  - Feature-map vectors 5
- Torsion Fingerprint Differences for comparing conformations 8

### Integration with other open-source projects

- KNIME: Workflow and analytics tool
- Django: “The web framework for perfectionists with deadlines”
- PostgreSQL: Extensible relational database
- Lucene: Text-search engine 1

### Usage by other open-source projects

- ChEMBL Beaker - standalone web server wrapper for RDKit and OSRA
- myChEMBL (blog post, paper) - A virtual machine implementation of open data and cheminformatics tools
- ZINC - Free database of commercially-available compounds for virtual screening
- sdf_viewer.py - an interactive SDF viewer
- sdf2ppt - Reads an SDFile and displays molecules as image grid in powerpoint/openoffice presentation.
- MolGears - A cheminformatics tool for bioactive molecules
- PYPL - Simple cartridge that lets you call Python scripts from Oracle PL/SQL.
- shape-it-rdkit - Gaussian molecular overlap code shape-it (from silicos it) ported to RDKit backend
- WONKA - Tool for analysis and interrogation of protein-ligand crystal structures
- OOMMPPAA - Tool for directed synthesis and data analysis based on protein-ligand crystal structures
- OCEAN - web-tool for target-prediction of chemical structures which uses ChEMBL as datasource
- chemfp - very fast fingerprint searching
- rdkit_ipynb_tools - RDKit Tools for the IPython Notebook
- chemicalite - SQLite integration for the RDKit
- Vernalis KNIME nodes
- Erlwood KNIME nodes
- AZOrange

## The Contrib Directory

The Contrib directory, part of the standard RDKit distribution, includes code that has been contributed by members of the community.

### LEF: Local Environment Fingerprints

Contains python source code from the publications:

- A. Vulpetti, U. Hommel, G. Landrum, R. Lewis and C. Dalvit, “Design and NMR-based screening of LEF, a library of chemical fragments with different Local Environment of Fluorine” J. Am. Chem. Soc. 131 (2009) 12949-12959. http://dx.doi.org/10.1021/ja905207t
- Vulpetti, G. Landrum, S. Ruedisser, P. Erbel and C. Dalvit, “19F NMR Chemical Shift Prediction with Fluorine Fingerprint Descriptor” J. of Fluorine Chemistry 131 (2010) 570-577. http://dx.doi.org/10.1016/j.jfluchem.2009.12.024

Contribution from Anna Vulpetti

### M_Kossner

Contains a set of pharmacophoric feature definitions as well as code for finding molecular frameworks.

Contribution from Markus Kossner

### PBF: Plane of best fit

Contribution from Nicholas Firth

Note as of the 2016.09.1 release this functionality is part of the RDKit core.

Contains C++ source code and sample data from the publication:

Firth, N. Brown, and J. Blagg, “Plane of Best Fit: A Novel Method to Characterize the Three-Dimensionality of Molecules” Journal of Chemical Information and Modeling 52 2516-2525 (2012). http://pubs.acs.org/doi/abs/10.1021/ci300293f

### mmpa: Matched molecular pairs

Python source and sample data for an implementation of the matched-molecular pair algorithm described in the publication:

Hussain, J., & Rea, C. “Computationally efficient algorithm to identify matched molecular pairs (MMPs) in large data sets.” Journal of chemical information and modeling 50 339-348 (2010). http://dx.doi.org/10.1021/ci900450m

Includes a fragment indexing algorithm from the publication:

Wagener, M., & Lommerse, J. P. “The quest for bioisosteric replacements.” Journal of chemical information and modeling 46 677-685 (2006).

Contribution from Jameed Hussain.

### SA_Score: Synthetic assessibility score

Python source for an implementation of the SA score algorithm described in the publication:

Ertl, P. and Schuffenhauer A. “Estimation of Synthetic Accessibility Score of Drug-like Molecules based on Molecular Complexity and Fragment Contributions” Journal of Cheminformatics 1:8 (2009)

Contribution from Peter Ertl

### fraggle: A fragment-based molecular similarity algorithm

Python source for an implementation of the fraggle similarity algorithm developed at GSK and described in this RDKit UGM presentation: https://github.com/rdkit/UGM_2013/blob/master/Presentations/Hussain.Fraggle.pdf

Contribution from Jameed Hussain

### pzc: Tools for building and validating classifiers

Contribution from Paul Czodrowski

### ConformerParser: parser for Amber trajectory files

Contribution from Sereina Riniker

Note as of the 2016.09.1 release this functionality is part of the RDKit core.

### NP_Score: Natural-product likeness score

Python source for an implementation of the NP score algorithm described in the publication:

“Natural Product Likeness Score and Its Application for Prioritization of Compound Libraries” Peter Ertl, Silvio Roggo, and Ansgar Schuffenhauer Journal of Chemical Information and Modeling 48:68-74 (2008) http://pubs.acs.org/doi/abs/10.1021/ci700286x

Contribution from Peter Ertl

### AtomAtomSimilarity: atom-atom-path method for fragment similarity

Python source for an implementation of the Atom-Atom-Path similarity method for fragments described in the publication:

Gobbi, A., Giannetti, A. M., Chen, H. & Lee, M.-L. “Atom-Atom-Path similarity and Sphere Exclusion clustering: tools for prioritizing fragment hits.” J. Cheminformatics 7 11 (2015). http://dx.doi.org10.1186/s13321-015-0056-8

Contribution from Richard Hall

## Footnotes

1: These implementations are functional but are not necessarily the best, fastest, or most complete.

2: Originally contributed by Andrew Dalke

3: Putta, S., Eksterowicz, J., Lemmen, C. & Stanton, R. “A Novel Subshape Molecular Descriptor” Journal of Chemical Information and Computer Sciences 43:1623–35 (2003).

4: Tosco, P., Balle, T. & Shiri, F. “Open3DALIGN: an open-source software aimed at unsupervised ligand alignment.” J Comput Aided Mol Des 25:777–83 (2011).

5: Landrum, G., Penzotti, J. & Putta, S. “Feature-map vectors: a new class of informative descriptors for computational drug discovery” Journal of Computer-Aided Molecular Design 20:751–62 (2006).

6: Nguyen, K. T., Blum, L. C., van Deursen, R. & Reymond, J.-L. “Classification of Organic Molecules by Molecular Quantum Numbers.” ChemMedChem 4:1803–5 (2009).

7: Riniker, S. & Landrum, G. A. “Similarity maps - a visualization strategy for molecular fingerprints and machine-learning methods.” Journal of Cheminformatics 5:43 (2013).

8: Schulz-Gasch, T., Schärfer, C., Guba, W. & Rarey, M. “TFD: Torsion Fingerprints As a New Measure To Compare Small Molecule Conformations.” J. Chem. Inf. Model. 52:1499–1512 (2012).

9: Riniker, S. & Landrum, G. A. “Better informed distance geometry: Using what we know to improve conformation generation.” J. Chem. Inf. Model. 55:2562–74 (2015).

## License

This document is copyright (C) 2013-2016 by Greg Landrum

This work is licensed under the Creative Commons Attribution-ShareAlike 4.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by-sa/4.0/ or send a letter to Creative Commons, 543 Howard Street, 5th Floor, San Francisco, California, 94105, USA.

The intent of this license is similar to that of the RDKit itself. In simple words: “Do whatever you want with it, but please give us some credit.”