chemical terms

8/3/2019 Chemical Terms

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Chemical Terms, a Language forCheminformatics

Gyrgy Pirok

American Chemical Society National Meeting, Chicago 2007


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Content

Problems to solve

Property calculations, the plugin system

The Chemical Terms language

Applications

Summary


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Problems to Solve

Filtering

Thousands of predictive calculations, topological indices,

and many "likeness" rules are published. Which ones ofthem should be supported by our database tools?

How could chemists combine these predictions duringstructure searching?

How could chemists use their existing propertycalculations inside ChemAxon tools?

How can we detect activated/deactivated sites,regioselectivity or potential side reactions?

How can chemists improve a virtual reaction ifit provides unfeasible products?

Virtual reactions


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Problems to Solve

Pharmacophore mapping

What pharmacophore types should we define?

Should we define pharmacophore types using functionalgroup lists or property calculations?

How to extend the definitions?

What goal function should we set?

How to define a custom goal functionincluding desired physicochemicalproperties?

Random evolutionary de Novo drug design


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The Chemical Terms Pyramid

Applications

Chemical TermsEvaluator

Plugin System

Property Calculations


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Property Calculations


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Plugins are Accessible

GUIs

command line tools

Java API

SQL Cartridge


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The Plugin System is Extensible

acceptor acceptorCount acceptorSiteCount acidicpKa acidicpKaLargeModelaliphaticAtom aliphaticAtomCount aliphaticBondCount aliphaticRingCountangle aromaticAtom aromaticAtomCount aromaticBondCountaromaticElectrophilicityOrder aromaticNucleophilicityOrderaromaticRingCount array asymmetricAtom asymmetricAtomCount atnoatomCount atomicPolarizability averagePolarizability balabanIndex basicpKabasicpKaLargeModel BCUT bond bondCount bondType canonicalResonantcanonicalTautomer carboaromaticRingCount carboRingCount chainAtomchainAtomCount chainBond chainBondCount charge chiralCenterchiralCenterCount composition conformer conformerCount conformersconnected connectedGraph connections count cxsmarts cxsmilescyclomaticNumber dihedral dissimilarity distance distanceDegree donordonorCount donorSiteCount dotDisconnectedFormuladoubleBondStereoisomer doubleBondStereoisomerCount

doubleBondStereoisomers dreidingEnergy eccentricityelectrophilicLocalizationEnergy enumeration enumerationCountenumerations exactMass field filter formalCharge formulafusedAliphaticRingCount fusedAromaticRingCount fusedRingCounthararyIndex hasValidConformer hydrogenCount heavyheteroaromaticRingCount heteroRingCount hyperWienerIndexisoelectricPoint isotopeComposition isotopeFormula largestAtomRingSizelargestRingSize logD logP logPIncrement logS logSMicro logSNeutrallogSTrue lowestEnergyConformer majorMicrospecies majorMs map massmatch matchCount max maxAtom maxValue microspeciesmicrospeciesCount microspeciesDistribution min minAtom minValuemolBinFormat molecularPolarizability molFormat molImage namenucleophilicLocalizationEnergy pair piChargeDensity piEnergy

piOrbitalElctronegativity pKa plattIndex polarizability property randicIndexrefractivity refractivityIncrements resonant resonantCount resonantsringAtom ringAtomCount ringBond ringBondCount ringCountringCountOfAtom rotatableBond rotatableBondCount shortestPathsigmaOrbitalElectronegativity smallestAtomRingSize smallestRingSizesmarts smiles solventAccessibleSurfaceArea sortAsc sortDesc stereoisomerstereoisomerCount stereoisomers stericEffectIndex stericHindrance sumszegedIndex tautomer tautomerCount tautomers tetrahedralStereoisomertetrahedralStereoisomerCount tetrahedralStereoisomerstopologicalPolarSurfaceArea totalChargeDensity traditionalNameuniqueSmiles valence vanDerWaalsSurfaceArea wienerIndex wienerPolarity


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Chemical Terms Function ExamplesSubstructure Matching

The query can be specified in file, or can be "inlined":

match("[#6:1][$([NX3:2](=[O:3])=[O:3]),$([NX3+:1](=[O:3])[O-:3])]" )

match("nitroquery.mol") // true if the query found in the

// current molecule

matchCount(aliphaticamine) // returns the number of aliphatic amino

// groups in the current molecule

Counting functional groups:

match(ratom(6),"[OH:1]C=[O:2]", 1, 2) // is the given reactant atom a

// carboxyl oxygen?

Matching a mapped atom of the functional group of a reactant in reactioncontext:

match(nitro) // true if the current molecule contains

// nitro group

Built-in dictionaries supporting named functional groups and reactions:

match(BeckmannRearrangement) // true if the current reaction is a

// rearrangement of an oxime to amide


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Function ExamplesChemical Calculations

Calculating physicochemical properties of the current molecule:

solventAccessibleSurfaceArea("7.4") // on pH 7.4

isoelectricPoint()

acidicpKa(ratom(4)) // the acidic pKa of the given reactant atom

Calculating physicochemical properties in reaction context:

electrophilicLocalizationEnergy(ratom(3))

logP(product(1)) // the logP of the given product

rotatableBondCount()

Calculating topological and geometrical descriptors:

SzegedIndex()

heteroAromaticRingCount()

hasValidConformer(product(1))

stericHindrance(ratom(7))

chiralCenterCount(ratom(7))


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Function ExamplesCalculations Returning Molecules

Predicting the major microspecies on the given pH

majorMicrospecies("7.0")

tautomer(1, "7.4") // dominant tautomer on the given pH

Determining resonant structures and tautomers of the current molecule

tautomers() // all tautomers

canonicalResonant() // canonical resonant structureresonants() // all resonant structures

Returning the stereoisomers of the given product in the current reaction

stereoIsomers(product(1))

Returning all enumerated molecules of a given Markush structure

enumeration()


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Combining functions in Chemical Terms

Creating complex descriptors for filtering:

(mass() >= 200) && (mass() = 2) &&

(rotatableBondCount()


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Combining functions in Chemical Terms

Identifying deactivated rings in virtual Friedel-Crafts acylation:

charge(ratom(1), "aromaticsystem") > -0.2

Determining the localization energy effect on regioselectivity in SEAr reactions:

electrophilicLocalizationEnergy (ratom(1))

Excluding reactants having sensitive groups in Friedel-Crafts acylation:

match(reactant(1),"[Cl,Br,I]C(=[O,S])C=C") ||

match(reactant(0), "[H][O,S]C=[O,S]") || match(reactant(0),"[P][H]") ||

(max(pka(reactant(0), filter(reactant(0), "match('[O,S;H1]')"),"acidic"))

> 14.5) ||(max(pka(reactant(0), filter(reactant(0), "match('[#7:1][H]',

1)"), "basic")) > 0)


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acceptorCount(product(1), "7.4")

name of the function

Molecule context Reaction context

acceptorCount("7.4")

name of the function

Chemical Terms Syntax and Context

parameters parameters

Parameters: molecule, atom, other custom parameters (e.g. pH)

Molecule context, used for single molecule inputmol(): refers to the current input molecule (can be omitted)

Reaction context, used for reaction input initiated by the Reactor:reactant(int i): refers to the i-th reactant (0-based indexing) product(int i): refers to the i-th product (0-based indexing)

ratom(int m): refers to the reactant atom corresponding to reactant atom map m according to thereaction equation

patom(int m): refers to the product atom corresponding to product atom map m according to the reactionequation

Additional contexts: atom context, search context


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The Chemical Terms Editor


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Applications

The problem


The Chemical Terms Language

Applications

Summary


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Applications of Chemical TermsCalculated Fields and Filters in Instant JChem


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Applications of Chemical TermsFilters in Pipeline Pilot


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Applications of Chemical TermsVirtual Reaction without Chemical Terms


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Applications of Chemical TermsReaction Editor - Encoding Reaction Rules


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Applications of Chemical TermsVirtual Reaction with Chemical Terms

Gyrgy Pirok, Nra Mt, Jen Varga, Jzsef Szegezdi, Mikls Vargyas, Szilrd Drnt, and Ferenc Csizmadia: Making "Real"Molecules in Virtual Space.J. Chem. Inf. Model.; 2006; 46(2) pp 563 - 568


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Applications of Chemical TermsHuman Xenobiotic Biotransformations


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Upcoming Features

simplified syntax replacing &&, ||, !with and, or, not

numbering base will be 1 universally

strongly typed parameters

simplified editing

syntax checker in editor

parameter dialogs in editor

more named functional groups in the dictionary

named reaction dictionary

new functionalities

functional group transformation queries in matching (carboxyl>>aldehide)

referring to database fields

conditional expressions (if)

IUPAC name functions

and more...


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Summary

The problem


The Chemical Terms Language

Applications

Summary


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Summary

What is Chemical Terms? A simple but extensible language to combine chemical functions for

various cheminformatics purposes A way to add more chemical "intelligence" to software programs A general interface for chemists to customize cheminformatics

applications

What is it good for? chemical data filtering creating complex SAR expressions making virtual reactions, biotransformations selective defining goal functions, termination criterias

defining pharmacophore types

and more...

How can I use it? Off the shelf (Reactor, Metabolizer, Instant JChem, command line) Integrate into own applications (Java/.NET API, Oracle Cartidge)

FREE for Academics


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Acknowledgements

Nra Mt, Zsolt MohcsiPlugin system, Chemical Terms Evaluator, Reactor, Pharmacophore mapping

Jzsef Szegezdi, Ferenc CsizmadiaProperty predictions, calculations

Istvn Cseh, Attila Szab

Chemical Terms Editor

Szilrd Drnt, Szabolcs CsepregiSubstructure searching functions, JChem Base integration, Pipeline Pilotintegration

Pter KovcsJChem Cartridge integration

Tim Dudgeon, Petr HamernikInstant JChem Integration

Mikls Vargyas

Pharmacophore mapping, Chemical Terms Evaluator

chemical terms

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