Scientific & technical presentation JChem Cartridge for Oracle version 5.3, January 2010 1 1 1

Contents Purpose of JChem Cartridge Features of JChem Cartridge Constituents of the JChem Cartridge API Normal Tables vs. JChem Tables Architecture of JChem Cartridge 2 2 2

Purpose of JChem Cartridge Access JChem functionality using SQL: SELECT count(*) FROM nci WHERE jc_contains(structure, 'Brc1cnc2ccccc12') = 1 Access JChem in any programming environment offering Oracle connectivity (.NET, Java, Perl, PHP, Python, Apache mod_plsql...)‏ Execute SQL queries efficiently using extensible indexes Precompute chemical information on structures by creating jc_idxtype indexes: CREATE INDEX jcxnci ON nci(structure) INDEXTYPE IS jc_idxtype The jc_idxtype implementation scans the indexed column for eligible structures in one single performance-optimized operation: domain index scan 3 3 3

Features of JChem Cartridge Adds chemistry knowledge into the SQL language of Oracle (SELECT, INSERT, UPDATE, ...)‏ Substructure, superstructure, full structure, similarity searching Complex chemical expressions using the Chemical Terms language that includes logP, pKa, ... Automatic property calculation during registration Standardization (canonicalization) during registration Structure format conversions (MRV, Molfile, SDfile, RDfile, SMILES, CML, etc.)‏; 2D, 3D image generation Structure enumeration using reaction rules User-defined fingerprint columns Custom similarity search through molecular descriptors Interaction with Oracle optimizer 4 4 4

Structure search features Wide range of query atoms Query properties R-group queries Full SMARTS support Coordination compounds Link nodes Pseudo atoms, lone pairs Relative stereo Reaction search features Hit coloring, position variation Polymers See detailed information on structure search: www.chemaxon.com/conf/Structural_Search.ppt 5

Search options Stereo on/off Ignore charge/isotope/radical/valence/mixture brackets Vague bond matching options Chemical Terms filter Tautomer search Inverse hit list Maximum search time / number of hits Combine with non-structure conditions Ordering of results etc. 6

Searching in Markush structures Combinatorial Markush structure registration and search Markush features handled in search & enumeration: R-groups (nesting to any depth) Atom lists, bond lists Position variation bond Link nodes and repeating units Homology groups Compatible Markush enumeration plugin Detailed description: http://www.chemaxon.com/jchem/doc/user/Query.html#combinatorialMarkush http://www.jchem.com/doc/user/Query.html#explH 7 7

Standardization Default standardization includes: Hydrogen removal Aromatization Custom standardization can be specified for each table or JChem index http://www.jchem.com/doc/user/Standardizer.html 8

Custom Standardization Example JChem Cartridge http://www.chemaxon.com/conf/Standardizer.ppt Custom Standardization Example before after 9

Compatibility and integration File formats: SMILES MDL molfile (v2000 and v3000)‏ MDL SDF RXN RDF MRV IUPAC name, InChI Markush DARC CDX Operating systems: Windows Linux Solaris HP-UX etc. DB engines: Oracle versions 9i R2 or above for alternative RDBMS systems, see the JChem Base presentation: http://www.chemaxon.com/JChem_Base.ppt 10

Elements of the JChem Cartridge API Operators (jc_...) for SQL and their functional forms (jcf package) for PL/SQL Parameters for index creation DML operators for JChem tables Support functions for user defined operators 11 11 11

Operators and functions I. Typical operator: jc_<some-operation>(<target-structure-column>, <some- operand>)‏ Operator for substructure search: jc_contains(<target-structure-column>, <query-structure>)‏ “Swiss-army-knife” search operator: jc_compare(<target-structure-column>, <query-structure>, <options>)‏ 12 12 12

Operators and functions II. Chemical Terms Over 100 built-in functions, including elemental analysis topological descriptors property predictions (logP/D, pKa, PSA, H bond donors/acceptors, charge etc). tautomers, protonation forms User-defined functions. Example: The Lipinski-rule in chemical terms SELECT count(*) FROM nci_3m WHERE jc_compare(structure, 'O=C1ONC(N1c2ccccc2)-c3ccccc3','sep=! t:s!ctFilter:(mass() <= 500) && (logP() <= 5) && (donorCount() <= 5) && (acceptorCount() <= 10)') = 1 13 13 13

Operators and functions III. jc_compare: substructure/similarity/exact searching combined with Chemical Terms expressions jc_matchcount: number of occurences of the query structure in the target jc_evaluate: Chemical Terms evaluation jc_molweight: molecular weight jc_formula: molecular formula jc_react: structure enumeration based on virtual reactions jc_standardize: structure canonicalization jc_molconvert: conversion to different formats (image generation is supported) jc_tanimoto: similarity search jcf.hitColorAndAlign: substructure coloring and alignment 14 14 14

Operators and functions IV. Similarity search example displaying ID, SMILES code, and molweight: SELECT cd_id, cd_smiles, cd_molweight FROM my_structures WHERE jc_tanimoto(cd_smiles, 'CC(=O)Oc1ccccc1C(O)=O') >= 0.8; Chemical Terms and Query Prefiltering: SELECT id, purchase_date FROM compounds_instock WHERE jc_compare(structure, 'C(=S)([N][N])[S]', 'sep=! t:t!simThreshold:0.9!ctFilter:logp()>1!filterQuery:SELECT rowid FROM compounds_instock WHERE purchase_date > DATE ''2002-01- 01''') = 1 Prefiltering allows to execute search on a subset of rows more efficiently. Dynamic generation of static images: SELECT jc_molconvertb(structure, 'png -2') FROM nci where id = :1 Avaliable image formats: png, jpeg, svg, ... PNG 15 15 15

Operators and functions V. Calculate logp: SELECT jc_evaluate('OC(=O)c1c2ccccc2nc3ccccc13', 'logp') FROM dual; Generate tautomers: SELECT jc_evaluate_x('NC1=C(CC=O)C=CCC1', 'chemTerms:tautomers() outFormat:smiles') FROM dual; Generate resonants: SELECT jc_evaluate_x('NC1=C(CC=O)C=CCC1', 'chemTerms:resonants() outFormat:smiles') FROM dual 16 16 16

Index parameters Index parameters affect: Examples: Fingerprint attributes Standardizer configuration Table space and storage options of the index table Examples: Standardization by stripping hydrogens and using basic aromatization: CREATE INDEX jcxnci ON nci(structure) INDEXTYPE IS jc_idxtype PARAMETERS('STD_CONFIG=removeexplicitH..aromatize:b')‏ Add structural keys to fingerprint for more efficient substructure searching (structural keys are defined in table stfp_keys): CREATE INDEX jcxnci ON nci(structure) INDEXTYPE IS jc_idxtype PARAMETERS('STRUCTURALFP_CONFIG=select structure from stfp_keys')‏ 17 17 17

Calls Not Using Indexes Using SQL statements for calling JChem operators on structures not stored in a table Sample SQL statement without index information: SELECT jc_contains('O=C1C=CNC=C1', 'n1ccccc1') FROM dual Setting default properties for calls not using indexes: CALL jc_set_default_property('standardizerConfig', 'aromatize:b')‏ 18 18 18

Supported Column Types VARCHAR2: typically for short formats, e.g. SMILES CLOB BLOB for longer formats, e.g. MDL molfile, Marvin (mrv)‏ 19 19 19

Supported Structure Table Types Regular Table: nci_1k JChem Table (generated by jcman or API): jc_nci_1k CREATE INDEX jcxnci_1k... Rowid of the base table (nci_1k)‏ Index table: jcxnci_1k_jcx CREATE INDEX jcxjc_nci_1k... 20 20 20

Regular Tables vs. JChem Tables Regular structure tables base table and index table are physically distinct index properties are specified as index parameters JChem structure tables base table and index table are physically the same most of the “index” properties are specified during table creation (jcman or Java API)‏ Pros & Cons: inserts from outside the database are faster with JChem tables JChem tables require Java API or the jcman command line tool (for table creation) and Java API or special cartridge functions for INSERTs, UPDATEs and DELETEs; standard SQL can be used with regular tables in all cases. 21 21 21

JChem Cartridge Architecture Computation intensive operations are performed in a separate Sun JVM. Advantage: fast execution (optimized native code)‏ flexibility in deployment JChem Server Oracle JChem Cartridge JChem Streams RMI JChem Base Search Update Cache Cache JDBC JChem Core 22 22 22

Performance Table containing 19,528,372 structures from PubChem with Intel Quad CPU Q6600 2.40GHz desktop PC, 8GB memory desktop PC Substructure search results: Query Structure Hit Count Time (ms)‏ C1CN1c2cnnc3c(cncc23)C4=CSC=C4 1487 O=C1ONC(N1c2ccccc2)c3ccccc3 129 823 Oc1c(N=N)c(cc2cc(ccc12)S(O)(=O)=O)S(O)(=O)=O 93 764 C(Sc1ncnc2ncnc12)c3ccccc3 489 786 NC1=CC=NC2=C1C=CC(Cl)=C2 6,001 1,189 c1ncc2ncnc2n1 146,256 6,665 Clc1ccccc1 2,975,285 82,646 JChem 5.2 23 23 23

Future plans Flexible 3D pharmacophore search R-Group decomposition Clustering Maximum common substructure search type Extended fingerprint connectivity (EFPC) 24 24 24

Summary JChem Cartridge for Oracle allows to access the rich functionality of JChem Base in a flexible and efficient manner. JChem Cartridge for Oracle uses creative solutions to broaden the applicability of JChem's core functions while preserving key benefits of the Java platform. 25 25 25

Links Documentation Forum Brochure www.jchem.com/doc/admin/cartridge.html www.jchem.com/doc/guide/cartridge/index.html Forum www.chemaxon.com/forum/ Brochure www.chemaxon.com/brochures/JChem_Cartridge.pdf 26 26 26

Visit other technical presentations MarvinSketch/View http://www.chemaxon.com/MarvinSketch_View.ppt MarvinSpace http://www.chemaxon.com/MarvinSpace.ppt Calculator Plugins http://www.chemaxon.com/Calculator_Plugins.ppt JChem Base http://www.chemaxon.com/JChem_Base.ppt JChem Cartridge http://www.chemaxon.com/JChem_Cartridge.ppt Standardizer http://www.chemaxon.com/Standardizer.ppt Screen http://www.chemaxon.com/Screen.ppt JKlustor http://www.chemaxon.com/JKlustor.ppt Fragmenter http://www.chemaxon.com/Fragmenter.ppt Reactor http://www.chemaxon.com/Reactor.ppt 27 27 27