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Chemoinformatics, Chemoinformatics, cheminformatics, chemical cheminformatics, chemical

informatics: What is it?informatics: What is it?

Gary Wiggins and Wendie ShreveGary Wiggins and Wendie Shreve

Chemistry LibraryChemistry Library

Indiana UniversityIndiana University

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AbstractAbstract

The terms “cheminformatics,” “chemiinformatics,” The terms “cheminformatics,” “chemiinformatics,” “cheminformatics,” and “chemical informatics” are “cheminformatics,” and “chemical informatics” are all used to describe a broad array of computer all used to describe a broad array of computer techniques and applications to solve chemistry techniques and applications to solve chemistry problems. We will look at the areas that comprise problems. We will look at the areas that comprise chemical informatics by examining the topics in chemical informatics by examining the topics in existing textbooks and other secondary sources. existing textbooks and other secondary sources. The identified topics will be mapped to the The identified topics will be mapped to the graduate courses in the Chemical Informatics graduate courses in the Chemical Informatics program at Indiana Universityprogram at Indiana University

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Dmitrii Ivanovich Mendeleev,Dmitrii Ivanovich Mendeleev,1834-19071834-1907

Discoverer of the Periodic Table—Discoverer of the Periodic Table—

An Early “Chemoinformatician”An Early “Chemoinformatician”

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Why Mendeleev?Why Mendeleev?

Faced with a large amount of data, with Faced with a large amount of data, with many gaps, Mendeleev:many gaps, Mendeleev: Sought patterns where none were obvious,Sought patterns where none were obvious, Made predictions about properties of Made predictions about properties of

unknown chemical substances, based on unknown chemical substances, based on observed properties of known substances,observed properties of known substances,

Created a great visualization tool!Created a great visualization tool!

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The Periodic Table of the The Periodic Table of the Elements by Mark WinterElements by Mark Winter

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Chemical Informatics: The New Chemical Informatics: The New “Handmaid” of Chemistry“Handmaid” of Chemistry

M.G. Mellon noted that Analytical Chemistry was M.G. Mellon noted that Analytical Chemistry was at one time considered the handmaid of at one time considered the handmaid of chemistry. (his chemistry. (his Chemical PublicationsChemical Publications, 5, 5thth ed.) ed.)

Handmaid (def) – Something that is necessarily Handmaid (def) – Something that is necessarily subservient or subordinate to another: subservient or subordinate to another: Ceremony is but the handmaid of worship. Ceremony is but the handmaid of worship. (Also, (Also, Handmaiden)Handmaiden)--Random House Unabridged Dictionary, 2--Random House Unabridged Dictionary, 2ndnd ed., 1993. ed., 1993.

Handmaid, maybe, but definitely not handmade!Handmaid, maybe, but definitely not handmade!

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What is Chemical Informatics?What is Chemical Informatics?

Chemical informatics helps chemists Chemical informatics helps chemists investigate new problems and organize investigate new problems and organize and analyze scientific data to develop and analyze scientific data to develop novel compounds, materials, and novel compounds, materials, and processes through the application of processes through the application of information technology.information technology.

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Cheminformatics, etc. in the Lit, Cheminformatics, etc. in the Lit, March 2000March 2000

Science Citation Index (Web of Science)

SciFinder Scholar

Bioinformatics 364 720Chemical Informatics 20 6Chemoinformatics included 7Chemiinformatics included 0Cheminformatics included 9

Term# Retrievals Containing Term

Prevalance of -informatics terms in the literature

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Cheminformatics, etc. in the Lit, Cheminformatics, etc. in the Lit, 31 July 200331 July 2003

Science Citation Index (Web of Science)

SciFinder Scholar

Bioinformatics 1830 5685Chemical Informatics 13 12Chemoinformatics 32 42Chemiinformatics 1 2Cheminformatics 30 56

Term# Retrievals Containing Term

Prevalance of -informatics terms in the literature

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Indiana University MS in Indiana University MS in Chemical InformaticsChemical Informatics

Major aspects of chemical informaticsMajor aspects of chemical informatics Information Acquisition:Information Acquisition: Methods for Methods for

generating and collecting data empirically generating and collecting data empirically (experimentation) or from theory (molecular (experimentation) or from theory (molecular simulation)simulation)

Information Management:Information Management: Storage and Storage and retrieval of informationretrieval of information

Information Use:Information Use: Data Analysis, correlation, Data Analysis, correlation, and application to problems in the chemical and application to problems in the chemical and biochemical sciencesand biochemical sciences

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UMIST MSc in CheminformaticsUMIST MSc in Cheminformatics

““This is a modular, one-year course which This is a modular, one-year course which provides high-level training in the handling provides high-level training in the handling of of chemical and biochemical informationchemical and biochemical information, , molecular modellingmolecular modelling and other aspects of and other aspects of cheminformatics.”cheminformatics.”

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University of Sheffield MSc in University of Sheffield MSc in Chemoinformatics ProgramChemoinformatics Program

““Chemoinformatics involves the application Chemoinformatics involves the application of IT to chemical data and includes topics of IT to chemical data and includes topics such as such as chemical databaseschemical databases, , combinatorial library designcombinatorial library design, , structure-structure-activity relationshipsactivity relationships and and structure-based structure-based drug designdrug design.”.”

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Sheffield’s Short CourseSheffield’s Short Course

Offered for the past three summers, in 4 Offered for the past three summers, in 4 days, emphasizes applications in modern days, emphasizes applications in modern drug discoverydrug discovery

Covers:Covers: 2D databases and database searching2D databases and database searching Diversity and compound selectionDiversity and compound selection Moving into 3D: experimental data sourcesMoving into 3D: experimental data sources Computational methods for 3DComputational methods for 3D

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Sheffield Short CourseSheffield Short Course

Coverage (continued):Coverage (continued): 3D databases3D databases Combinatorial librariesCombinatorial libraries Analysis of high-throughput screening Analysis of high-throughput screening

datadata

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Graduate Courses in Chemical Graduate Courses in Chemical Informatics at Indiana UniversityInformatics at Indiana University

C571 Chemical Information TechnologyC571 Chemical Information Technologyhttp://www.indiana.edu/~cheminfo/C571/571home.htmlhttp://www.indiana.edu/~cheminfo/C571/571home.html

C572 Molecular Modeling & C572 Molecular Modeling & Computational ChemistryComputational Chemistryhttp://www.indiana.edu/~cheminfo/C572/572home.htmlhttp://www.indiana.edu/~cheminfo/C572/572home.html

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JCICS – Major Research AreasJCICS – Major Research Areas

Chemical InformationChemical Information Text SearchingText Searching Structure and Substructure SearchingStructure and Substructure Searching DatabasesDatabases PatentsPatents

George W.A. MilneGeorge W.A. Milne

C571 LectureC571 Lecture

Fall 2002Fall 2002

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JCICS – Major Research AreasJCICS – Major Research Areas

Chemical ComputationChemical Computation Quantum MechanicsQuantum Mechanics Statistics (regression, neural nets, etc.)Statistics (regression, neural nets, etc.) QSAR, QSPRQSAR, QSPR Graph TheoryGraph Theory DNA ComputingDNA Computing

George W.A. MilneGeorge W.A. Milne

C571 LectureC571 Lecture

Fall 2002Fall 2002

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JCICS – Major Research AreasJCICS – Major Research Areas

Molecular ModelingMolecular Modeling 3D Structure Generation3D Structure Generation 3D Searching (pharmacophores)3D Searching (pharmacophores) Docking Docking

George W.A. MilneGeorge W.A. Milne

C571 LectureC571 Lecture

Fall 2002Fall 2002

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JCICS – Major Research AreasJCICS – Major Research Areas

Biopharmaceutical Computation Biopharmaceutical Computation Drug DesignDrug Design Combinatorial ChemistryCombinatorial Chemistry Protein and Enzyme StructureProtein and Enzyme Structure Membrane StructureMembrane Structure ADME-related ResearchADME-related Research

George W.A. MilneGeorge W.A. Milne

C571 LectureC571 Lecture

Fall 2002Fall 2002

2020

George W.A. MilneGeorge W.A. MilneC571 Lecture, Fall 2002C571 Lecture, Fall 2002

Desirable Skills for Chemistry GradsDesirable Skills for Chemistry Grads

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Frank Brown’s DefinitionFrank Brown’s Definition

……the mixing of information resources to the mixing of information resources to transform data into information and transform data into information and information into knowledge, for the information into knowledge, for the intended purpose of making decisions intended purpose of making decisions faster in the arena of drug lead faster in the arena of drug lead identification and optimisation.identification and optimisation.

Brown, F.K. “Chemoinformatics, what it is and how does it Brown, F.K. “Chemoinformatics, what it is and how does it impact drug discovery.” Annual Reports in Medicinal Chemistry, impact drug discovery.” Annual Reports in Medicinal Chemistry, 1998, 33, 375-384.1998, 33, 375-384.

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Application of Cheminformatics Application of Cheminformatics in the Drug Industryin the Drug Industry

The computer is used to analyze the The computer is used to analyze the interactions between the drug and the interactions between the drug and the receptor site and design molecules with an receptor site and design molecules with an optimal fit.optimal fit.

Once targets are developed, libraries of Once targets are developed, libraries of compounds are screened for activity with compounds are screened for activity with one or more relevant assays using High one or more relevant assays using High Throughput Screening.Throughput Screening.

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Application of Cheminformatics Application of Cheminformatics in the Drug Industryin the Drug Industry

Hits are then evaluated for binding, Hits are then evaluated for binding, potency, selectivity, and functional activity.potency, selectivity, and functional activity.

Seeking to improve:Seeking to improve: PotencyPotency AbsorptionAbsorption DistributionDistribution MetabolismMetabolism EliminationElimination

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Some Methods and ToolsSome Methods and Tools

Structure/Activity RelationshipsStructure/Activity Relationships

Genetic AlgorithmsGenetic Algorithms

Statistical Tools (e.g., recursive pairing)Statistical Tools (e.g., recursive pairing)

Data Analysis ToolsData Analysis Tools

VisualizationVisualization

Hardware DevelopmentsHardware Developments

Chemically-Aware Web Language (CML)Chemically-Aware Web Language (CML)

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CAS Indexing of a Relevant CAS Indexing of a Relevant ArticleArticle

““The impact of informatics and The impact of informatics and computational chemistry on synthesis and computational chemistry on synthesis and screening.” Manly, Charles J.; Louise-screening.” Manly, Charles J.; Louise-May, Shirley; Hammer, Jack D. Drug May, Shirley; Hammer, Jack D. Drug Discovery Today (2001), 6(21), 1101-Discovery Today (2001), 6(21), 1101-1110.1110.

A review with 87 referencesA review with 87 references

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Controlled Vocabulary Indexing Controlled Vocabulary Indexing of the Manly Articleof the Manly Article

ChemistryChemistryHigh throughput screeningHigh throughput screeningDrug screeningDrug screeningBioinformaticsBioinformaticsCombinatorial chemistryCombinatorial chemistryDrug designDrug designMolecular modelingMolecular modelingPharmacokineticsPharmacokineticsCombinatorial libraryCombinatorial library

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Informatics Components (per Informatics Components (per Dow Chemical Visitors)Dow Chemical Visitors)

ArchitectureArchitecture

LIMSLIMS ComponentsComponents

of anof an

InformaticsInformatics

SystemSystem

Electronic Electronic Records MgmtRecords Mgmt

SubstanceSubstance

RegistryRegistry

Process Data Process Data MgmtMgmt

Integration & Integration & User User

InterfaceInterface

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Chemical R&D vs. Chemical R&D vs. Pharmaceutical R&DPharmaceutical R&D

Much smaller number of substances tested in a Much smaller number of substances tested in a weekweekMuch larger number of tests to considerMuch larger number of tests to considerAnswers tend to come in shades of gray rather than Answers tend to come in shades of gray rather than yes or noyes or noTargets change frequently in chemical R&DTargets change frequently in chemical R&DMust integrate a large variety of sources that were Must integrate a large variety of sources that were not designed for integrationnot designed for integrationNew approach to taxonomy is needed.New approach to taxonomy is needed.

--L. David Rothman--L. David RothmanThe Dow Chemical Co.The Dow Chemical Co.

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Characteristics of a Chemical Characteristics of a Chemical Informatics Faculty MemberInformatics Faculty Member

Appreciates the value of algorithmsAppreciates the value of algorithms

Is interested in data mining, data Is interested in data mining, data modeling, and relational database systemsmodeling, and relational database systems

Pays attention to searching issues and the Pays attention to searching issues and the literatureliterature

Has compatability and commonality with Has compatability and commonality with bioinformatics researchbioinformatics research

Is able to talk to computer scientists.Is able to talk to computer scientists.

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Major JournalsMajor Journals

Journal of Chemical Information and Computer Journal of Chemical Information and Computer Sciences (ACS)Sciences (ACS)

Journal of Molecular Graphics and Modelling Journal of Molecular Graphics and Modelling (Elsevier)(Elsevier)

Journal of Combinatorial Chemistry (ACS)Journal of Combinatorial Chemistry (ACS)

Journal of Proteome Research (ACS)Journal of Proteome Research (ACS)

Proteomics (Wiley-VCH)Proteomics (Wiley-VCH)

Molecular and Cellular Proteomics (ASBMB)Molecular and Cellular Proteomics (ASBMB)

Acta Crystallographica (IUCr)Acta Crystallographica (IUCr)

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TextbooksTextbooks

Leach, Andrew R.; Gillet, Valerie J. An Leach, Andrew R.; Gillet, Valerie J. An Introduction to Chemoinformatics. Kluwer, Introduction to Chemoinformatics. Kluwer, 2003. ISBN 1-4020-1347-72003. ISBN 1-4020-1347-7

Engel, Thomas. Chemoinformatics: A Engel, Thomas. Chemoinformatics: A Textbook. Wiley-VCH, expected date of Textbook. Wiley-VCH, expected date of publication: August 2003. ISBN 3-527-publication: August 2003. ISBN 3-527-30681-130681-1

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Reference WorksReference Works

Encyclopedia of Computational Chemistry, Schleyer, P. von R.; Encyclopedia of Computational Chemistry, Schleyer, P. von R.; Allinger, N.L.; Clark, T.; Gasteiger, J.; Kollman, P.A.; Schaefer, H.F.; Allinger, N.L.; Clark, T.; Gasteiger, J.; Kollman, P.A.; Schaefer, H.F.; Shreiner, P.R. (Eds.). 5 v. Wiley, Chichester, 1998.Shreiner, P.R. (Eds.). 5 v. Wiley, Chichester, 1998.

Gasteiger, Johann J., ed. Handbook of Chemoinformatics: From Gasteiger, Johann J., ed. Handbook of Chemoinformatics: From Data to Knowledge. 4 v. Wiley-VCH, expected date of publication Data to Knowledge. 4 v. Wiley-VCH, expected date of publication August 2003. ISBN 3-527-30680-3August 2003. ISBN 3-527-30680-3

Reviews in Computational Chemistry. Wiley-VCH, 1990-Reviews in Computational Chemistry. Wiley-VCH, 1990-

Paris, Greg. Bibliography: Chemical Information Retrieval and 3D Paris, Greg. Bibliography: Chemical Information Retrieval and 3D Searching. Searching. http://panizzi.shef.ac.uk/cisrg/links/grep/chemDB.4.html http://panizzi.shef.ac.uk/cisrg/links/grep/chemDB.4.html

SIRCh: Chemical Informatics Home Page at Indiana University SIRCh: Chemical Informatics Home Page at Indiana University http://http://www.indiana.edu/~cheminfo/informatics/cinformhome.htmlwww.indiana.edu/~cheminfo/informatics/cinformhome.html

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ConclusionConclusion

Chemical Informatics is an evolving field Chemical Informatics is an evolving field with many facets.with many facets.

It will become increasingly important in It will become increasingly important in areas of chemistry outside the drug areas of chemistry outside the drug industry.industry.

It will play an increasing role in the It will play an increasing role in the developing area of proteomics.developing area of proteomics.

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BibliographyBibliographyBrown, F.K. “Chemoinformatics, what it is and how does it impact drug Brown, F.K. “Chemoinformatics, what it is and how does it impact drug discovery.” Annual Reports in Medicinal Chemistry, 1998, 33, 375-384.discovery.” Annual Reports in Medicinal Chemistry, 1998, 33, 375-384.Glen, Robert. “Developing tools and standards in molecular informatics.” Glen, Robert. “Developing tools and standards in molecular informatics.” Chemical Communications, 2002, (23), 2745-2747.Chemical Communications, 2002, (23), 2745-2747.Hann, Mike; Green, Richard. “Chemoinformatics—a new name for an old Hann, Mike; Green, Richard. “Chemoinformatics—a new name for an old problem?” Current Opinion in Chemical Biology, 1979, 3, 379-383.problem?” Current Opinion in Chemical Biology, 1979, 3, 379-383.Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. “Experimental and Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. “Experimental and computational approaches to estimate the solubility and permeability in drug computational approaches to estimate the solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, discovery and development settings. Advanced Drug Delivery Reviews, 1997, 23, 3-15.1997, 23, 3-15.Rosso, Eugene. “Chemistry plans a structural overhaul.” Nature Rosso, Eugene. “Chemistry plans a structural overhaul.” Nature (Naturejobs) 12 September 2002, 419(6903). (Naturejobs) 12 September 2002, 419(6903).

http://www.nature.com/naturejobs/careersandrecruitment/2002.html http://www.nature.com/naturejobs/careersandrecruitment/2002.html

Rothman, L. David. “Information management for research in the chemical Rothman, L. David. “Information management for research in the chemical industry.” Abstracts of Papers, 223rd ACS National Meeting, Orlando, FL, industry.” Abstracts of Papers, 223rd ACS National Meeting, Orlando, FL, United States, April 7-11, 2002 (2002), CINF-044.United States, April 7-11, 2002 (2002), CINF-044.Smith, Chris. “Cheminformatics: Redefining the crucible.” The Scientist, Smith, Chris. “Cheminformatics: Redefining the crucible.” The Scientist, 2002, 16(8), 40.2002, 16(8), 40.