1. Structural Search Using ChemAxon Tools
Szabolcs Csepregi
JChem version 5.3, April 2010

2. 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
Applications of structural search: R-group decomposition, Standardizer, Reactor, Pmapper, Fragmenter
Future plans
All examples were generated by Marvin

3. 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
JChemBase JSP example:
Jcsearch user’s guide:
API Documentation:
Search classes:
chemaxon.sss.search.Search
chemaxon.sss.search.MolSearch
chemaxon.jchem.db.JChemSearch
Instant JChem
JChem For Excel

4. Structural search type
Search types in JChem
Structural search type
Query
Result
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

5. 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 5

6. Hit coloring and alignment

7. 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):

8. Query features 2. Query properties
Symbol
Description
H<n>
Total hydrogen count a
Aromatic A
Aliphatic
R<n>
Ring count in SSSR
r<n>
Ring size in SSSR
v<n>
Valence
X<n>
Connectivity
D<n>
Degree
h<n>
Implicit H count
rb<n> rb*
Ring bond count *: as drawn
s<n> s*
Substitution count *: as drawn u
Unsaturated atom

9. Query features 3. Atomic SMARTS features
SMARTS atoms:
Additional query properties:
Example:
Carbonyl C, but not amide
Symbol
Description
& ; , !
Logical operators
$(<smarts>)
Recursive smarts
+0, -0
Zero charge

10. Query features 4. Homology atoms
Can be used:
In queries against molecule and reaction tables.
In Markush structures
Built-in and user-defined groups

11. 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
Symbol
Description
- = #
Single, double, triple :
aromatic
& , ; !
Logical operators @
Ring bond
/ \ /? \?
Directional bond (cis/trans)
Symbol
Description
(C.C)
Same component
(C).(C)
Different component
C.C
No component restrictions

12. Coordination compounds
Atom-to-atom (dative) and multicenter coordinate bonds Alternative representations: Position variation bond

13. Hydrogens H representations: Example: Explicit Implicit Query H count:
total (H<n>)
implicit (h<n>)
Example:
Considered in ABAS
Explicit H
Implicit H
Query H count
Query
Target
Target
Query

14. Stereo searching 1. Double bonds
Not cis
Not trans
Cis or trans
(unknown)
Trans
Cis
Meaning
Depiction
Levels of check:
All
Only marked double bonds (MDL: stereo care flag)
None

15. Stereo searching 2. Tetrahedral chirality
Stereo bond types:
Relative stereo configuration
Chiral flag model
Enhanced stereo representation: AND<n>, OR<n>, ABS groups
Up or down
Down Up

16. 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:

17. Reaction search Reactants, agents, products
Transformation recognition (mapping)
Stereospecific reactions (inversion, retention)
Reactant grouping
Reacting center

18. R-group search Scaffold, R-group definitions
Monovalent, divalent R-groups
R-logic
Occurrence
If-then
Rest H

19. Undefined R-atoms
- No substitution elsewhere
retrieves:

20. 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

21. 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
Lipinski rule of 5
(mass() <= 500) && (logP() <= 5) && (donorCount() <= 5) &&
(acceptorCount() <= 10);
Veber filter
(rotatableBondCount() <= 10) &&
(PSA() <= 140);

22. Markush structure registration and search
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

23. 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
JChem table
Hits for the query
Search
query
Fingerprint screening
Need to be searched
Screened out
Atom by atom
search
Results

24. 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

25. Further applications of structural search in JChem
Transformations - Standardizer & Reactor
Identification of pharmacophoric groups - Pmapper nitro: amidine:
Identification of bond cleavage - Fragmenter
ether cut:
Converting covalent form of alcoholates to ionic form:
Enamine-amine tautomerism:

26. Duplicates not checked
Performance
Query
Number of hits
Search time 2
0.91 s 93
0.98 s
6,001
1.30 s
146,256
5,66 s
Substructure searching in 19.5 million structures (Pubchem) JChem Base 5.2.2, Intel Quad Q GHz, 8 GB RAM; Oracle
Compound registration:
Number of compounds
Elapsed time
Duplicates not checked
Duplicates checked
10,000
21 s
26 s
100,000
2 min 4 s
2 min 34 s
200,000
4 min 24 s
5 min 13 s

27. 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)

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

29. References
JChem Query Guide
Chemical Terms reference
JChem Base JSP demo page
Jcsearch command line tool
API documentation
(chemaxon.sss.search.MolSearch, chemaxon.jchem.db.JChemSearch)
JChem Base
JChem Cartridge
Instant JChem
JChem for Excel

30. Thank you for your attention
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