Standardizer Molecular Cosmetics for Chemoinformatics György Pirok Nóra Máte István Cseh Szilárd Dóránt Péter Kovács Szabolcs Csepregi Ferenc Csizmadia

Why standardize structures? Canonicalisation Uniformization of structures without changing the chemical content to recognize duplicates, functional groups (aromatization, mesomers, tautomers,... ) Beautification Making the structures visually more attractive ( dearomatization, cleaning coordinates, wedge orientation,... ) Modification Conversion of structures by modifying its original content as a preparation step for further chemoinformatics tasks (transformations, removing stereo, removing R-groups,...). often difficult to categorize the standardization actions

Canonicalisation making hydrogens explicit converting to canonical mesomer form transforming to user defined mesomer form Hydrogens aromatizing Kekülé rings Resonant structures converting to canonical tautomer form removing user defined fragments transforming to user defined tautomer form Tautomers expanding stoichiometry Other removing small fragments making hydrogens implicit setting the chiral flag

Mesomers

Tautomers oxo-enol, enamine-imine

Tautomers pyridone-pyridol

Fragment removal

Specific counterion removal

Solvent removal

Stoichiometry expansion expanding salt stoichiometry

Stoichiometry expansion expanding reaction stoichiometry

Beautification calculating 2D coordinates Hydrogens converting aromatic rings to Kekülé format Resonant structures making hydrogens implicit Cleaning reallocating wedge bonds contracting/expanding/ ungrouping abbreviated and multiple groups Groups template based cleaning 3D geometry optimization

Template-based Cleaning 2D-coordinate calculation of macrocycles or bridged systems

query Template-based Cleaning aligning search results to the query

client Canonicalization During Database Import Relational Database input structures canonicalization configurationoriginal structurescanonicalized structures server Standardizer JChem Base / Cartridge

client Sending Query to the Database Relational Database server query structure canonicalization configurationcanonicalized query query is compared to the canonicalized structures Standardizer JChem Base / Cartridge

Displaying Result Structures Relational Database original structures server client beautification configuration beautified structures Standardizer JChem Base / Cartridge

Modification custom transformations +

API and command line interface Standardizer st = new Standardizer(new File("standardize.xml")); st.standardize(mol); standardize input.sdf -c config.xml -o output.smiles

Live Demonstration

Applications: Virtual Synthesis

Applications: Structure Databases

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Acknowledments Ferenc Csizmadia Nóra Máté István Cseh Szabó Attila Szilárd Dóránt Péter Kovács Szabolcs Csepregi