ORganic VIrtual LibraryORganic VIrtual LibraryORganic VIrtual LibraryORganic VIrtual LibraryORganic VIrtual LibraryORganic VIrtual LibraryORganic VIrtual LibraryORganic VIrtual LibraryA program to create Virtual Compound Library using Organic SubstituentsA program to create Virtual Compound Library using Organic SubstituentsA program to create Virtual Compound Library using Organic SubstituentsA program to create Virtual Compound Library using Organic Substituents

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What it is all What it is all What it is all What it is all What it is all What it is all What it is all What it is all aboutaboutaboutabout ????????

Generation of large number of compounds = Generation of large number of compounds = Generation of large number of compounds = Generation of large number of compounds = LibraryLibraryLibraryLibrary

Focused on Focused on Focused on Focused on Organic Substituents Organic Substituents Organic Substituents Organic Substituents (200 in no.)(200 in no.)(200 in no.)(200 in no.)

Only most frequentOnly most frequentOnly most frequentOnly most frequent organic substituentsorganic substituentsorganic substituentsorganic substituents

2 Types: Non2 Types: Non2 Types: Non2 Types: Non----AromaticAromaticAromaticAromatic AromaticAromaticAromaticAromatic

CH3 Cl

CH3 RRRRRRRR

BasementBasementBasementBasementSMILES (Simplified Molecular Input Line Entry System)SMILES (Simplified Molecular Input Line Entry System)SMILES (Simplified Molecular Input Line Entry System)SMILES (Simplified Molecular Input Line Entry System): is a line notation (a : is a line notation (a : is a line notation (a : is a line notation (a typographical method using printable characters) for entering and typographical method using printable characters) for entering and typographical method using printable characters) for entering and typographical method using printable characters) for entering and representing molecules and reactions.representing molecules and reactions.representing molecules and reactions.representing molecules and reactions.

Why SMILES is chosen ?Why SMILES is chosen ?Why SMILES is chosen ?Why SMILES is chosen ?

§Easy to storage and retrievalEasy to storage and retrievalEasy to storage and retrievalEasy to storage and retrieval

§Requires minimum storage space in hard disksRequires minimum storage space in hard disksRequires minimum storage space in hard disksRequires minimum storage space in hard disks

§ReproducibilityReproducibilityReproducibilityReproducibility

§String manipulation can be done which can be easily reflected in 3DString manipulation can be done which can be easily reflected in 3DString manipulation can be done which can be easily reflected in 3DString manipulation can be done which can be easily reflected in 3D

Focus & ScopeFocus & ScopeFocus & ScopeFocus & Scope

§No Diverse Compounds = No Diverse Compounds = No Diverse Compounds = No Diverse Compounds = Molecular Diversity MinimumMolecular Diversity MinimumMolecular Diversity MinimumMolecular Diversity Minimum

§Maintain ScaffoldMaintain ScaffoldMaintain ScaffoldMaintain Scaffold

§Play with Side Chains / TerminalsPlay with Side Chains / TerminalsPlay with Side Chains / TerminalsPlay with Side Chains / Terminals

§Creating Analogues Creating Analogues Creating Analogues Creating Analogues §Creating Analogues Creating Analogues Creating Analogues Creating Analogues

§Requires priori knowledgeRequires priori knowledgeRequires priori knowledgeRequires priori knowledge of substitution in SMILEof substitution in SMILEof substitution in SMILEof substitution in SMILE

§Library Generation based on Well Furnished Substitution Site; Not onLibrary Generation based on Well Furnished Substitution Site; Not onLibrary Generation based on Well Furnished Substitution Site; Not onLibrary Generation based on Well Furnished Substitution Site; Not on

ScaffoldScaffoldScaffoldScaffold

§Deals with Deals with Deals with Deals with Organic SubsetOrganic SubsetOrganic SubsetOrganic Subset : B,C,N,O,P,S: B,C,N,O,P,S: B,C,N,O,P,S: B,C,N,O,P,S

AdvantagesAdvantagesAdvantagesAdvantages

§Freely availableFreely availableFreely availableFreely available

§Command line interpreter InterfaceCommand line interpreter InterfaceCommand line interpreter InterfaceCommand line interpreter Interface

§Execution across all platformsExecution across all platformsExecution across all platformsExecution across all platforms

§Customizable PERL program for own library creationCustomizable PERL program for own library creationCustomizable PERL program for own library creationCustomizable PERL program for own library creation

§Output files in .smi format (SMILES), easily recognized by molecular editorsOutput files in .smi format (SMILES), easily recognized by molecular editorsOutput files in .smi format (SMILES), easily recognized by molecular editorsOutput files in .smi format (SMILES), easily recognized by molecular editors

§Generate a Library of 1200 unique moleculesGenerate a Library of 1200 unique moleculesGenerate a Library of 1200 unique moleculesGenerate a Library of 1200 unique molecules

§Useful for HTS and FragmentUseful for HTS and FragmentUseful for HTS and FragmentUseful for HTS and Fragment----based approachbased approachbased approachbased approach

LimitationsLimitationsLimitationsLimitations

§No GUINo GUINo GUINo GUI

§No atoms other than Organic Subset (e.g. Silicon) since their occurrence isNo atoms other than Organic Subset (e.g. Silicon) since their occurrence isNo atoms other than Organic Subset (e.g. Silicon) since their occurrence isNo atoms other than Organic Subset (e.g. Silicon) since their occurrence is

known to be very lessknown to be very lessknown to be very lessknown to be very less

§Users who want to customize must know the structure’s SMILEUsers who want to customize must know the structure’s SMILEUsers who want to customize must know the structure’s SMILEUsers who want to customize must know the structure’s SMILE

(It can be easily tackled by Molecular Editors)(It can be easily tackled by Molecular Editors)(It can be easily tackled by Molecular Editors)(It can be easily tackled by Molecular Editors)

Minimum RequirementsMinimum RequirementsMinimum RequirementsMinimum RequirementsActive Perl 5.10 (Freeware Active Perl 5.10 (Freeware Active Perl 5.10 (Freeware Active Perl 5.10 (Freeware http://www.ActiveState.com/ActivePerl/http://www.ActiveState.com/ActivePerl/http://www.ActiveState.com/ActivePerl/http://www.ActiveState.com/ActivePerl/) ) ) )

Hardware Space Required:Hardware Space Required:Hardware Space Required:Hardware Space Required:Generates 60.8 KB of 1200 library files (if your files are compressed byGenerates 60.8 KB of 1200 library files (if your files are compressed byGenerates 60.8 KB of 1200 library files (if your files are compressed byGenerates 60.8 KB of 1200 library files (if your files are compressed byGeneric Windows Compression)Generic Windows Compression)Generic Windows Compression)Generic Windows Compression)

AlgorithmAlgorithmAlgorithmAlgorithmAlgorithmAlgorithmAlgorithmAlgorithmStructure Input as SMILEStructure Input as SMILEStructure Input as SMILEStructure Input as SMILE

Substitute with 200 Organic SubstituentsSubstitute with 200 Organic SubstituentsSubstitute with 200 Organic SubstituentsSubstitute with 200 Organic Substituents

Functional Group in 200 Organic Functional Group in 200 Organic Functional Group in 200 Organic Functional Group in 200 Organic Substituents marked by the letter ‘X’Substituents marked by the letter ‘X’Substituents marked by the letter ‘X’Substituents marked by the letter ‘X’

SubstituteSubstituteSubstituteSubstitute Functional Group with Functional Group with Functional Group with Functional Group with Organic Subset (B,C,N,O,P,S) Organic Subset (B,C,N,O,P,S) Organic Subset (B,C,N,O,P,S) Organic Subset (B,C,N,O,P,S)

Generate a Virtual Library comprising 1200 moleculesGenerate a Virtual Library comprising 1200 moleculesGenerate a Virtual Library comprising 1200 moleculesGenerate a Virtual Library comprising 1200 molecules

© Prasanth Kumar, (2010), ORVIL : ORganic Virtual Library© Prasanth Kumar, (2010), ORVIL : ORganic Virtual Library© Prasanth Kumar, (2010), ORVIL : ORganic Virtual Library© Prasanth Kumar, (2010), ORVIL : ORganic Virtual Library

CH3

Tamoxifen’s SMILESTamoxifen’s SMILESTamoxifen’s SMILESTamoxifen’s SMILES

Region of SubstitutionRegion of SubstitutionRegion of SubstitutionRegion of Substitution

Input Format

CN(Cl)CCOc1ccc(cc1)/C(c2ccccc2)=C(/CC)c3ccccc3

SSSSCCCCAAAAFFFFFFFFOOOO

O

NCH3

CH3

Tamoxifen (Breast Cancer Drug)Tamoxifen (Breast Cancer Drug)Tamoxifen (Breast Cancer Drug)Tamoxifen (Breast Cancer Drug)

Input Format

CN(Cl)CCOc1ccc(cc1)/C(c2ccccc2)=C(region)c3ccccc3

Use the word Use the word Use the word Use the word REGIONREGIONREGIONREGION or or or or regionregionregionregionin order to recognize the place in order to recognize the place in order to recognize the place in order to recognize the place of organic substituents of organic substituents of organic substituents of organic substituents substitutionsubstitutionsubstitutionsubstitution

OOOOLLLLDDDD

Let us generate an Organic Virtual Library of Let us generate an Organic Virtual Library of TamoxifenTamoxifen

Command line interpreter Interface of ORVILCommand line interpreter Interface of ORVILCommand line interpreter Interface of ORVILCommand line interpreter Interface of ORVIL

.txt .smi .txt .pl

CN(Cl)CCOc1ccc(cc1)/C(c2ccccc2)=C(region)c3ccccc3CN(Cl)CCOc1ccc(cc1)/C(c2ccccc2)=C(region)c3ccccc3CN(Cl)CCOc1ccc(cc1)/C(c2ccccc2)=C(region)c3ccccc3CN(Cl)CCOc1ccc(cc1)/C(c2ccccc2)=C(region)c3ccccc3

= (6 atoms * 137 Non= (6 atoms * 137 Non= (6 atoms * 137 Non= (6 atoms * 137 Non----Aromatic Org. Subs. = 822 files) Aromatic Org. Subs. = 822 files) Aromatic Org. Subs. = 822 files) Aromatic Org. Subs. = 822 files) + 4 program files + 4 program files + 4 program files + 4 program files

ClO

Cl

Cl

ApplicationsApplicationsApplicationsApplications

CH3

N

ClO

ONCH3

CH3

Fareston C-Compound #3

ReferencesReferencesReferencesReferences

Uwe Eichlera, Peter Ertla, Alberto Gobbia and Bernd Rohdeb, 1999. Uwe Eichlera, Peter Ertla, Alberto Gobbia and Bernd Rohdeb, 1999. Uwe Eichlera, Peter Ertla, Alberto Gobbia and Bernd Rohdeb, 1999. Uwe Eichlera, Peter Ertla, Alberto Gobbia and Bernd Rohdeb, 1999. Definition of an Optimal Subset of Organic Substituents. Interactive Visual Definition of an Optimal Subset of Organic Substituents. Interactive Visual Definition of an Optimal Subset of Organic Substituents. Interactive Visual Definition of an Optimal Subset of Organic Substituents. Interactive Visual Comparison of Various Selection Algorithms. Internet Journal of Chemistry, Comparison of Various Selection Algorithms. Internet Journal of Chemistry, Comparison of Various Selection Algorithms. Internet Journal of Chemistry, Comparison of Various Selection Algorithms. Internet Journal of Chemistry, 2(14).2(14).2(14).2(14).

Perl Programming by James TindallPerl Programming by James TindallPerl Programming by James TindallPerl Programming by James TindallPerl Programming by James TindallPerl Programming by James TindallPerl Programming by James TindallPerl Programming by James Tindall

Marvin Family, Markush Enumerations, ChemAxon LtdMarvin Family, Markush Enumerations, ChemAxon LtdMarvin Family, Markush Enumerations, ChemAxon LtdMarvin Family, Markush Enumerations, ChemAxon Ltd

ChemSketch, ACDLabsChemSketch, ACDLabsChemSketch, ACDLabsChemSketch, ACDLabs

(Entire List will be available in Manuscript)(Entire List will be available in Manuscript)(Entire List will be available in Manuscript)(Entire List will be available in Manuscript)

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