Java Solutions for Cheminformatics

ChemAxon JChem Oracle Cartridge and related toolkits

April 2007

ChemAxon thumbnailCompany• Founded in 1998, based in Budapest, Hungary, representation in the US,

UK and Japan• Wide cheminformatics expertise (>30 staff) 9 PhD, 11 MSc• Wide industry expertise >200 corporate clients + >800 academic usersProducts• Cheminformatics tools - structure drawing, visualization, search,

transformation, library profiling and property prediction• Enterprise chemistry database and cartridge technologyTechnology• Powerful/Flexible – Enterprise API toolkits• Solutions – Desktop applications• Java based + .NET – Platform & database independent + Web ready • Dedicated Oracle Cartridge and Oracle integration from applicationsMantra• Do what they want, respond quickly

Toolkit and applications overview

Available from Oracle SQL & integrated with Oracle

Product development philosophy

Client driven development

Fast and reliable support>1000 active clients

Sophisticated technology

High performance (speed, accuracy, features)

Rounded, industry relevant functionality

Customizable

Extendable

Long term relevance

Comprehensive API

Platform independence (Java)

JChem Cartridge

Generating pKa and logD values by an SQL statement

Features of JChem Cartridge

• Adds chemistry knowledge into the SQL language of Oracle (SELECT, INSERT, UPDATE, ...)

• Substructure, superstructure, exact structure, structure and reaction similarity searching

• Fast: typically 1K hits in 3M structures within a second, fast index creation, row insertion & deletion

• Complex chemical expressions using the Chemical Terms language (>100 functions available)

• Standardization (canonicalization) during registration and querying

• Structure format conversions (MRV, Molfile, SDfile, RDfile, SMILES, CML, etc.)

• Dynamic 2D, 3D image generation• Structure enumeration using reaction rules yielding

‘synthetically feasible’ structures

Operators and functions – highlights I

“Swiss-army-knife” search operator:

jc_compare(<target-structure-column>, <query-structure>, <options>)

Chemical Terms: Over 100 built-in functions + user-defined functions.

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

Example: Lipinski-rule in expressed in chemical terms

Operators and functions – highlights II

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, pdf, emf ...

Indexes and column types

Index parameters can effect:• Fingerprint attributes• Standardizer configuration• Table space and storage options of the index table

CREATE INDEX jcxnci ON nci(structure) INDEXTYPE IS jc_idxtype PARAMETERS('STD_CONFIG=dehydrogenize:optional..aromatize:d')

Supported column types• VARCHAR2• CLOB• BLOB

Performance

• Index creation (regular structure tables): 5,801 sec• Import w/o duplicate filtering (JChem structure tables): 13,104 sec

• Substructure search results:

60,45915,873

1,987980

1,017456

364

274,356Clc1ccccc149,848c1ncc2ncnc2n1

4,632[#7]C1=CC=NC2=C1C=CC(Cl)=C21,752C(Sc1ncnc2ncnc12)c3ccccc31,188[#8]-c1c(N=N)c(cc2cc(ccc12)S([#8])(=O)=O)S([#8])(=O)=O

204O=C1ONC(N1c2ccccc2)c3ccccc3

0C1CN1c2cnnc3c(cncc23)C4=CSC=C4

Time (ms)Hit CountQuery Structure

Test platform: Table containing 3,003,012 structures in VARCHAR2 columns with 4 year old 3GHz dual Xeon (Netburst architecture) with 2GB system memory

Canonicalization with Standardizer

• Aromatize/dearomatize (ChemAxon and Daylight type rules)

• Add/remove explicit hydrogens

• Convert mesomers / tautomers / functional groups

• Removesolventscounterions by listsmallest fragmentretain largest fragment

• Set/Remove chiral flag, remove stereofeatures

• Ungroup S groups

• Enumerate by stoichiometry values

• 2D, 3D coordinate generation (cleaning)

• Template based cleaning

Virtual Synthesis with Reactor

Effective– focused, combinatorial

and diverse libraries– combinatorial, random

and exhaustive dispatching

– high throughput

Flexible� memory, file and database

operations sequential or combinatorial mode

� compound or reaction output type� reverse direction

Compatible– reactions: MRV, RXN, RDF,

SMARTS/SMIRKS – compounds: MRV, MOL, SDF, SMILES– mapping: ChemAxon, Daylight,

automapper

Smart– chemo-, regio- and stereospecific– customizable

Instant JChem: http://www.chemaxon.com/conf/Instant_JChem.ppt

Instant JChem

Desktop application for local and remote chemical database management, search and structure based prediction

• Simple connect to Oracle and MySQL external databases

• Powerful search functionalities

• Scalable – explore ’000,000’s+ live structures

• Dynamically predict propertiesusing Calculator Plugins

• Apply canonicalization rules forimport and viewing

• Form builder

• Relational data support

• Wide import / export options

• Library overlap analysis

• Very active development –what do you want to do?

JChem Cartridge – current developments

• Pharmacophore similarity search, custom descriptor (e.g. BCUT, ~ scalar) and metric at similarity search

• Markush functionality• Coordinated bond search (ferrocene)• Query tables• JChem Server, JChem cluster• Enhanced cartridge administration GUI (web-based)

Find out more

• Product descriptions & links– www.chemaxon.com/products.html

• Forum - open access (no secrets) & very active– www.chemaxon.com/forum

• Presentations and posters– www.chemaxon.com/conf

• Download– www.jchem.com/licensefrset.html

Contacts US

Douglas DrakeSan Diego, CA858 254 1264ddrake@chemaxon.com

Alex AllardyceBoston, MA

857 544 0541aa@chemaxon.com

David HatchOkemos MI

517 381 5181dhatch@chemaxon.com