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

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Presentation on theme: "Slide 1 Structural Search Using ChemAxon Tools JChem version 5.3 Structural Search Using ChemAxon Tools Szabolcs Csepregi 1 JChem version 5.3, April 2010."— Presentation transcript:

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

2 Slide 2 Structural Search Using ChemAxon Tools JChem version 5.3 Structural Search Using ChemAxon Tools 2 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 Slide 3 Structural Search Using ChemAxon Tools JChem version 5.3 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 Instant JChem JChem For Excel 3

4 Slide 4 Structural Search Using ChemAxon Tools JChem version 5.3 Search types in JChem 4 Atom By Atom Search or structural search: Similarity search: – Different Descriptors – Different Metrics MC(E)S – maximum common (edge) substructure Duplicate Full structure Superstructure Substructure ResultQueryStructural search type

5 Slide 5 Structural Search Using ChemAxon Tools JChem version 5.3 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 Search options 55

6 Slide 6 Structural Search Using ChemAxon Tools JChem version 5.3 Hit coloring and alignment 6

7 Slide 7 Structural Search Using ChemAxon Tools JChem version 5.3 Query features 1. Atomic features 7 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 Slide 8 Structural Search Using ChemAxon Tools JChem version 5.3 Query features 2. Query properties 8 SymbolDescription H Total hydrogen count aAromatic AAliphatic R Ring count in SSSR r Ring size in SSSR v Valence X Connectivity D Degree h Implicit H count rb rb*Ring bond count *: as drawn s s*Substitution count *: as drawn uUnsaturated atom

9 Slide 9 Structural Search Using ChemAxon Tools JChem version 5.3 Query features 3. Atomic SMARTS features 9 SMARTS atoms: Additional query properties: Example: Carbonyl C, but not amide SymbolDescription & ;, !Logical operators $( )Recursive smarts +0, -0Zero charge

10 Slide 10 Structural Search Using ChemAxon Tools JChem version 5.3 Query features 4. Homology atoms Can be used: –In queries against molecule and reaction tables. –In Markush structures Built-in and user-defined groups 10

11 Slide 11 Structural Search Using ChemAxon Tools JChem version 5.3 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 11 SymbolDescription - = #Single, double, triple :aromatic &, ; !Logical operators @Ring bond / \ /? \?Directional bond (cis/trans) SymbolDescription (C.C)Same component (C).(C)Different component C.CNo component restrictions

12 Slide 12 Structural Search Using ChemAxon Tools JChem version 5.3 Coordination compounds Atom-to-atom (dative) and multicenter coordinate bonds. Alternative representations:Position variation bond 12

13 Slide 13 Structural Search Using ChemAxon Tools JChem version 5.3 Hydrogens 13 H representations: – Explicit – Implicit – Query H count: – total (H ) – implicit (h ) Example: Considered in ABAS Explicit HImplicit HQuery H count Query Target Query

14 Slide 14 Structural Search Using ChemAxon Tools JChem version 5.3 Stereo searching 1. Double bonds Levels of check: –All –Only marked double bonds (MDL: stereo care flag) –None 14 Not cis Not trans Cis or trans (unknown) Trans Cis MeaningDepiction

15 Slide 15 Structural Search Using ChemAxon Tools JChem version 5.3 Stereo searching 2. Tetrahedral chirality 15 Stereo bond types: Relative stereo configuration Chiral flag model Enhanced stereo representation: AND, OR, ABS groups Up or downDownUp

16 Slide 16 Structural Search Using ChemAxon Tools JChem version 5.3 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: 16

17 Slide 17 Structural Search Using ChemAxon Tools JChem version 5.3 Reaction search Reactants, agents, products Transformation recognition (mapping) Stereospecific reactions (inversion, retention) Reactant grouping Reacting center 17

18 Slide 18 Structural Search Using ChemAxon Tools JChem version 5.3 R-group search 18 Scaffold, R-group definitions Monovalent, divalent R-groups R-logic Occurrence If-then Rest H

19 Slide 19 Structural Search Using ChemAxon Tools JChem version 5.3 Undefined R-atoms 19 - No substitution elsewhere retrieves:

20 Slide 20 Structural Search Using ChemAxon Tools JChem version 5.3 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 20

21 Slide 21 Structural Search Using ChemAxon Tools JChem version 5.3 Chemical Terms filter 21 Lipinski rule of 5 (mass() <= 500) && (logP() <= 5) && (donorCount() <= 5) && (acceptorCount() <= 10); Veber filter (rotatableBondCount() <= 10) && (PSA() <= 140); 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

22 Slide 22 Structural Search Using ChemAxon Tools JChem version 5.3 Markush structures 22 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 Slide 23 Structural Search Using ChemAxon Tools JChem version 5.3 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 23 JChem table Hits for the query Search query Fingerprint screening Need to be searched Screened out Atom by atom search Results

24 Slide 24 Structural Search Using ChemAxon Tools JChem version 5.3 Application: R-group decomposition 24 JChem is able to identify the ligands of a given scaffold at specified substitution positions: Query(scaffold) Result Library R-group decomposition

25 Slide 25 Structural Search Using ChemAxon Tools JChem version 5.3 Further applications of structural search in JChem Transformations - Standardizer & Reactor Identification of pharmacophoric groups - Pmapper nitro:amidine: Identification of bond cleavage - Fragmenter ether cut: 25 Enamine-amine tautomerism: Converting covalent form of alcoholates to ionic form:

26 Slide 26 Structural Search Using ChemAxon Tools JChem version 5.3 Performance 26 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 QueryNumber of hitsSearch time 20.91 s 930.98 s 6,0011.30 s 146,2565,66 s Number of compounds Elapsed time Duplicates not checked Duplicates checked 10,00021 s26 s 100,0002 min 4 s2 min 34 s 200,0004 min 24 s5 min 13 s Compound registration:

27 Slide 27 Structural Search Using ChemAxon Tools JChem version 5.3 Future plans 27 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 Slide 28 Structural Search Using ChemAxon Tools JChem version 5.3 Summary 28 JChem suite: contains a broad range of chemical search facilities, including Markush structure analysis. Structural search is a useful tool for many applications.

29 Slide 29 Structural Search Using ChemAxon Tools JChem version 5.3 References 29 JChem Query Guide http://www.chemaxon.com/jchem/doc/user/Query.html http://www.chemaxon.com/jchem/doc/user/Query.html Chemical Terms reference http://www.chemaxon.com/jchem/marvin/help/chemicalterms/ChemicalTerms.html 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 http://www.chemaxon.com/jchem/examples/db_search/index.jsp Jcsearch command line tool http://www.chemaxon.com/jchem/doc/user/Jcsearch.html http://www.chemaxon.com/jchem/doc/user/Jcsearch.html API documentation http://www.chemaxon.com/jchem/doc/api/index.html http://www.chemaxon.com/jchem/doc/api/index.html (chemaxon.sss.search.MolSearch, chemaxon.jchem.db.JChemSearch) JChem Base http://www.chemaxon.com/product/jc_base.html http://www.chemaxon.com/product/jc_base.html JChem Cartridge http://www.chemaxon.com/product/jc_cart.html http://www.chemaxon.com/product/jc_cart.html Instant JChem http://www.chemaxon.com/product/ijc.html http://www.chemaxon.com/product/ijc.html JChem for Excel http://www.chemaxon.com/products/jchem-for-excel/ http://www.chemaxon.com/products/jchem-for-excel/

30 Slide 30 Structural Search Using ChemAxon Tools JChem version 5.3 30 Thank you for your attention Máramaros köz 3/a Budapest, 1037 Hungary info@chemaxon.com www.chemaxon.com


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