Chemoinformatics and Metabolism

Paula de Matos

EBI is an Outstation of the European Molecular Biology Laboratory.

Chemoinformatics and Metabolism Group
Research

Indexing, searching
Natural Products and and dissemination of
Metabolomics chemical information

Cheminformatics Algorithms and Toolkits

 Chemical Entities of Biological Interest
• A database containing a freely available,
manually annotated dictionary of molecular
entities focused on ‘small’ chemical
compounds.

• Provides a method to navigate the

chemical space via an ontology

• ChEBI aims to provide a central, definitive

reference of chemical nomenclature.

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 http://www.ebi.ac.uk/chebi

Dictionary
Ontology

Resource for
Nomenclature

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 What does ChEBI cover?

• Mostly small entities

• Big entities too like

• alumina
• amylose
• metaborate

Excludes proteins and nucleic acids

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 Status

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 ChEBI further info
• http://www.ebi.ac.uk/chebi

• Mailing lists:
• chebi-help@ebi.ac.uk
• chebi-announce@lists.sourceforge.net
• chebi-ontology@lists.sourceforge.net

• Submitting data
• http://www.ebi.ac.uk/chebi/submissions

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The Chemistry Development Kit (CDK):
An Open Source Java-Library for Structural Chemo- and Bioinformatics

•>90.000 Lines of Code, >900 Classes, > 9000 Methods

•Library Generation
•Virtual Screening
•Molecular Property Prediction
•Visualization

http://cdk.sourceforge.net

(1) Steinbeck, C.; Hoppe, C.; Kuhn, S.; Guha, R.; Willighagen, E. L. Current Pharmaceutical Design 2006, 12, 2111-2120.
(2) Steinbeck<, C.; Han, Y. Q.; Kuhn, S.; Horlacher, O.; Luttmann, E., Willighagen, E. Journal of Chemical Information and
Computer Sciences 2003, 43, 493-500.
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The Chemistry Development Kit (CDK)
Input/Output Visualization
•I/O (CML, MDL Molfile, SDF, PDB) •Structure-Diagram-Layout (SDG)
•SMILES •2D Rendering
•InChI •3D Rendering

Modelling Library Enumeration

•3D Model-Builder •Deterministic Isomer generator
•Atom-Typing •Stochastic Structure Generators via
•Force-Field •Simulated Annealing
•Representation of Biomolecular Structures •Genetic Algorithms

Chemical Graphs Properties

•Isomorphism detection •Fingerprinting
•Maximum-Common-Substructure Searches •> 70 QSAR-Descriptors
•SMARTS- and Substructure searches •QSAR model building
•Ring searches
•Aromaticity detection
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Example: Structure Diagram Generation

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Example: Fingerprinting
H
N

IMolecule superstructure = MoleculeFactory.makeIndole();

IMolecule substructure = MoleculeFactory.makePyrrole();
O
Fingerprinter fingerprinter = new Fingerprinter(); O
BitSet superBS = fingerprinter.getFingerprint(superstructure);
BitSet subBS = fingerprinter.getFingerprint(substructure);
boolean isSubset = FingerprinterTool.isSubset(superBS, subBS);

Bitscreen coding for structural features

0 0 1 1 0 1 0 0 1 0

O O
-COOH Alky Hetero-
aryl N O-Alkyl -NH2
H N
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 CDK in numbers

•
67 registered developers on SF
•
86 people subscribed to cdk-devel list
•
111 people subscribed to cdk-user list

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 CDK in numbers

80,966 downloads since 2001

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 CDK in numbers

CDK article (2003)

cited 68 times
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 CDK info
• Project home page:
• http://cdk.sourceforge.net/

• Mailing list:
• cdk-user@lists.sourceforge.net
• cdk-devel@lists.sourceforge.net

• Documentation
• http://pele.farmbio.uu.se/nightly/

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 OrChem

• Oracle chemistry plug-in using the

Chemistry Development Kit (CDK).

• OrChem is suitable for Oracle 11G and onwards

• Uses Oracle’s JIT compiler

• Not an Oracle data cartridge - it doesn't need Oracle's

extensibility architecture because its Java components run
as Java stored procedures inside the Oracle standard JVM
(Aurora).

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 OrChem database structure

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 Example OrChem Queries
• Similarity search
• select * from table(
orchem_simsearch.search( 'OC4=C(C(=C3OC(C)
(COC=1C=CC(=CC=1)CC2C(=O)NC(=O)S2)CCC3=C4C)C)C','S
MILES',0.8,null,'N')
);

• Substructure search
• select orchem_subsearch.search(molfile,'MOL',50,'Y') from
compounds where molregno=12345;

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 Fingerprint distribution

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 Parallel vs. Non parallel
Performance of substructure search on 3.5 million compounds

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 Substructure benchmarking
Performance of substructure search on 3.5 million compounds

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 Similarity Benchmarking

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 OrChem info
• http://orchem.sourceforge.net/

• Mailing list:
• orchem-devel@lists.sourceforge.net

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