Structural Search Using ChemAxon Tools

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Structural Search Using ChemAxon Tools

• Szabolcs Csepregi

JChem version 5.3, April 2010
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Structural Search Using ChemAxon Tools
Interfaces Search types and options Query
features, Stereo searching Special search types
reaction, R-group search, Chemical Terms
filters Searching against Combinatorial Markush
structures Fingerprint screening Performance Appli
cations of structural search R-group
decomposition, Standardizer, Reactor, Pmapper,
Fragmenter Future plans All examples were
generated by Marvin
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Structural search interfaces

• Example web GUI-s
• JSP (Java Server Pages)
• AJAX example Javascript and JChem Web Services
• Command line jcsearch
• Java and .NET API
• MolSearch class in memory
• JChemSearch class in database
• Cartridge Oracle SQL
• JChem Web Services

• Instant JChem
• JChem For Excel

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Search types in JChem
Result
Query
Structural search type

• Atom By Atom Search or structural search
• Similarity search
• Different Descriptors
• Different Metrics

Substructure
Superstructure
Full structure
Duplicate
MC(E)S maximum common (edge) substructure
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Search options

• Some selected structure search options
• Stereo on/off/diastereomers
• Ignore charge/isotope/radical/valence/polymers,
  etc.
• Vague bond matching options
• Chemical Terms filter
• Tautomer search (even in substructure search)
• Inverse hit list
• Maximum search time / number of hits
• Combine with non-structure conditions
• Ordering of results
• Similarity type / metric

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Hit coloring and alignment
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Query features 1. Atomic features

• Query atom types
• any(A, AH)
• hetero (Q, QH)
• list, not list
• metal (M, MH)
• halogen (X, XH)
• periodic table groups (G1-18)
• Pseudo atoms e.g. Resin
• Explicit lone pairs (match to implied lone
  pairs as well.)
• Charge, isotope, radical
• Link nodes (repeatable)

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Query features 2. Query properties
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Query features 3. Atomic SMARTS features

• SMARTS atoms
• Additional query properties
• Example
• Carbonyl C, but not amide

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Query features 4. Homology atoms

• Can be used
• In queries against molecule and reaction tables.
• In Markush structures
• Built-in and user-defined groups

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Query features 5. Bond features components

• Query bond types Any, single or double, single
  or aromatic, double or aromatic
• Bond topology chain/ring
• Smarts bonds
• Component level grouping

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Coordination compounds

• Atom-to-atom (dative) and multicenter coordinate
  bonds.Alternative representations Positio
  n variation bond

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Hydrogens

• H representations
• Explicit
• Implicit
• Query H count
• total (Hltngt)
• implicit (hltngt)
• Example

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Stereo searching 1. Double bonds

• Levels of check
• All
• Only marked double bonds (MDL stereo care flag)
• None

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Stereo searching 2. Tetrahedral chirality

• Stereo bond types
• Relative stereo configuration
• Chiral flag model
• Enhanced stereo representation ANDltngt, ORltngt,
  ABS groups

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Groups integration (query target)

• Both sides are treated similarly by the search
• Abbreviations (super-atom S-groups)
• Multiple groups
• Other S-groups supported component, mixture,
  formulation , many polymer brackets

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Reaction search

• Reactants, agents, products
• Transformation recognition (mapping)
• Stereospecific reactions (inversion, retention)
• Reactant grouping
• Reacting center

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R-group search

• Scaffold, R-group definitions
• Monovalent, divalent R-groups
• R-logic
• Occurrence
• If-then
• Rest H

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Undefined R-atoms

• - No substitution elsewhere
• retrieves

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Polymer storage and search

• Comprehensive representation
• Source based and structure based
• Copolymer types, mixtures, ladder-type polymers,
  etc
• Phase shifting
• End groups specific, undefined, etc.
• Flexible
• Attached data search
• Wide range of polymer search options

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Chemical Terms filter

• Chemically aware filtering for structure and
  similarity searches
• Elements of the Chemical Terms language
• structure matching functions (describing
  functional groups, reaction sites, similarity,
  etc)
• property calculations (partial charge
  distribution, pKa, logP, HB donors, acceptors,
  topological descriptors, etc)
• arithmetic and logic-operators
• Examples

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Markush structures

• Markush structure registration and search
• Markush features
• R-groups
• Atom lists, bond lists
• Position variation bond
• Link nodes and repeating units
• Homology groups
• Compatible enumeration plugin

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Fingerprint screening in the database

• JChem database searches use fingerprint
  technology for fastest search results.
• It rapidly filters out most non-hits -usually
  more than 99 of them are rejected.
• Supported fingerprint types
• Chemical hashed fingerprints
• User-defined additional structural keys
• Average screening time in a 3-million cached
  table 0.1s

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Application R-group decomposition
JChem is able to identify the ligands of a given
scaffold at specified substitution
positions Query(scaffold) Result Library
R-group decomposition
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Further applications of structural search in JChem

• Transformations - Standardizer Reactor
• Identification of pharmacophoric groups -
  Pmapper nitro amidine
• Identification of bond cleavage - Fragmenter
• ether cut

Enamine-amine tautomerism
Converting covalent form of alcoholates to ionic
form
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Performance
Substructure searching in 19.5 million structures
(Pubchem) JChem Base 5.2.2, Intel Quad Q6600
2.4GHz, 8 GB RAM Oracle 10.2.0.3
Compound registration
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Future plans

• R-group decomposition GUI in client applications
• Visualization of similarity search results using
  MCS
• Diastereomer search
• Markush search enhancements (homology variation
  conditions, maximum common substructure, etc)

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Summary

• JChem suite contains a broad range of
  chemical search facilities, including Markush
  structure analysis.
• Structural search is a useful tool for many
  applications.

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References

• JChem Query Guide http//www.chemaxon.com/jchem/d
  oc/user/Query.html
• Chemical Terms reference http//www.chemaxon.com/
  jchem/marvin/help/chemicalterms/ChemicalTerms.html
  
• JChem Base JSP demo page http//www.chemaxon.com/
  jchem/examples/db_search/index.jsp
• Jcsearch command line tool http//www.chemaxon.
  com/jchem/doc/user/Jcsearch.html
• API documentation http//www.chemaxon.com/jchem/d
  oc/api/index.html
• (chemaxon.sss.search.MolSearch,
  chemaxon.jchem.db.JChemSearch)
• JChem Base http//www.chemaxon.com/product/jc_bas
  e.html
• JChem Cartridge http//www.chemaxon.com/product/j
  c_cart.html
• Instant JChem http//www.chemaxon.com/product/ijc
  .html
• JChem for Excel http//www.chemaxon.com/products/
  jchem-for-excel/

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Thank you for your attention
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