1 Szabolcs Csepregi*, Szilárd Dóránt, Nóra Máté, Miklós Vargyas, Péter Kovács, György Pirok, Ferenc Csizmadia First presented at Applications of Cheminformatics and Chemical Modelling to Drug Discovery · 8-19 Nov 2004 Updated. April, 2005 Structural Search Using ChemAxon Tools
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1 Szabolcs Csepregi*, Szilárd Dóránt, Nóra Máté, Miklós Vargyas, Péter Kovács, György Pirok, Ferenc Csizmadia First presented at Applications of Cheminformatics.
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Szabolcs Csepregi*, Szilárd Dóránt, Nóra Máté, Miklós Vargyas, Péter Kovács, György Pirok, Ferenc Csizmadia
First presented at Applications of Cheminformatics and Chemical Modelling to Drug Discovery · 8-19 Nov 2004 Updated. April, 2005
Structural Search Using ChemAxon Tools
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Contents
Structural search in cheminformatics
The JChem suite of tools
Structural search in JChem• Interfaces
• Database solutions: JChemBase, Cartridge
• Standardization
• Search features
MCS/MCES and Library MCS
R-group decomposition
The Chemical Terms language
Future plans
All examples generated by ChemAxon’s Marvin
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Structural search in cheminformatics
A few examples to highlight the diversity of applications. :
•Compound registration – duplicate checking
•Database search e.g. imidazole derivatives
•Pharmacophoric group identification (JChem Screen, JKlustor)
•Functional group identification
•Cleavage bond identification (JChem Fragmenter)
•Virtual reaction processing (JChem Reactor)
•Standardization (canonicalization of structures, JChem Standardizer)
•Toxical fragment identification (superstructure search)
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Search types in JChem
• ABAS(Atom By Atom Search) or structural search:– Exact– Substructure– Superstructure– MC(E)S – maximum common (edge) substructure– R-group decomposition (identify ligands of a given scaffold)
• Similarity search:– Different Descriptors– Different Metrics
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ABAS search interfaces
• JSP(Java Server Pages): web GUI for database– Similarity & structural search– Substructure highlighting– Additional constraints– Insert, modify, delete
• Command line utility: jcsearch: for files and DB
• Java API– isMatching() – Only to check matching– findFirst(), findNext() Enumerate all– findAll() possible matchings
• Cartridge: access all functionality from SQL
• Chemical Terms
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ABAS options
• General options:• Order sensitive hits e.g.• Pre-assignment of query and target atoms• Consider stereo or not, absolute stereo (ignore chiral flag)• Timeout limit• Exact charge/radical/isotope/query features/bond/stereo matching• Double bond stereo: no check/marked/all double bonds• Chemical Terms filter expression• etc
• Database search:• Maximum search time/number of hits• Additional SQL SELECT expression for prefiltering• Output table• Reverse hits mode
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Structural search in database
• Search: two stage method:– Rapid pre-screening based on chemical hashed fingerprints– ABAS (isMatching)
• Duplicate check at compound registration:– Hash code: primary filter– ABAS (isMatching)
• Standardization• Caching of structures and fingerprints allow top performance
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Import with JChem Base Manager
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Chemical Terms
Some available functions
• Structural search (match, matchcount)• Partial charge distribution • pKa, Log P, Log D, major microspecies• Polarizability• Topological Polar Surface Area• Number of rotatable bonds, rings, aromatic rings, etc.• Number of HB donors/acceptors• Exact mass • Arithmetic and logic operators • Extensible: your own Java plugins can be easily added.
• Etc.
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Future plans
• More query features (e.g link nodes, ring bond count, unsaturated atom)
• Flexible search options: tautomeric search, ignore bond types, salts, etc.
• Search targets having R-groups (Markush structures)
• etc.
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Summary
Structural search provides a useful set of tools for chemists and cheminformaticians.
ChemAxon JChem suite contains a broad range of chemical search facilities and the presented benchmark results illustrate the high performance of JChem search.
The new Chemical Terms language is a beneficial complement to structural searches allowing data mining made easy.
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Links
• Home page– www.chemaxon.com
• Forum– www.chemaxon.com/forum
• Animated demos and tutorials– www.chemaxon.com/demos
• Presentations and posters– www.chemaxon.com/conf
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