chemical information -...

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JCICS JCICS –– Major Research AreasMajor Research Areas

Chemical InformationChemical InformationText SearchingText Searching

Structure and Substructure SearchingStructure and Substructure Searching

DatabasesDatabases

PatentsPatents

George W.A. MilneGeorge W.A. Milne

C571 LectureC571 Lecture

Fall 2002Fall 2002

22


Chemical ComputationChemical ComputationQuantum MechanicsQuantum Mechanics

Statistics (regression, neural nets, etc.)Statistics (regression, neural nets, etc.)

QSAR, QSPRQSAR, QSPR

Graph TheoryGraph Theory

DNA ComputingDNA Computing



Fall 2002Fall 2002

33


Molecular ModelingMolecular Modeling3D Structure Generation3D Structure Generation

3D Searching (pharmacophores)3D Searching (pharmacophores)

Docking Docking



Fall 2002Fall 2002

44


Biopharmaceutical Computation Biopharmaceutical Computation Drug DesignDrug Design

Combinatorial ChemistryCombinatorial Chemistry

Protein and Enzyme StructureProtein and Enzyme Structure

Membrane StructureMembrane Structure

ADMEADME--related Researchrelated Research



Fall 2002Fall 2002

55

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

Desirable Skills for Chemistry GradsDesirable Skills for Chemistry Grads

66

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 identification and optimisationoptimisation..

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Application of Application of Cheminformatics 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.

88

Application ofApplication of Cheminformatics 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

ChemicallyChemically--Aware Web Language (CML)Aware Web Language (CML)

1010

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.; Louisescreening.” Manly, Charles J.; Louise--May, Shirley; Hammer, Jack D. Drug May, Shirley; Hammer, Jack D. Drug Discovery Today (2001), 6(21), 1101Discovery Today (2001), 6(21), 1101--1110.1110.

A review with 87 referencesA review with 87 references

1111

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)

Integration & Integration & User User

InterfaceInterface

Process Data Process Data MgmtMgmt

SubstanceSubstance

RegistryRegistry

Electronic Electronic Records MgmtRecords Mgmt

ComponentsComponents

of anof an

InformaticsInformatics

SystemSystem

LIMSLIMS

ArchitectureArchitecture

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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 Answers tend to come in shades of gray rather than yes or nothan yes or noTargets change frequently in chemical R&DTargets change frequently in chemical R&DMust integrate a large variety of sources that Must integrate a large variety of sources that were not designed for integrationwere not designed for integrationNew approach to taxonomy is needed.New approach to taxonomy is needed.

----L. David RothmanL. 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 Has compatability compatability and commonality with 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 Journal of Molecular Graphics and Modelling Modelling (Elsevier)(Elsevier)

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

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

Proteomics (WileyProteomics (Wiley--VCH)VCH)

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

Acta Crystallographica Acta Crystallographica ((IUCrIUCr))

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Forthcoming BooksForthcoming Books

Leach, Andrew R.; Leach, Andrew R.; GilletGillet, Valerie J. An Introduction to , Valerie J. An Introduction to ChemoinformaticsChemoinformatics. . KluwerKluwer, expected date of publication: , expected date of publication: June 2003.June 2003.

GasteigerGasteiger, Johann J., ed. Handbook of , Johann J., ed. Handbook of ChemoinformaticsChemoinformatics: From Data to Knowledge. 4 v. Wiley: From Data to Knowledge. 4 v. Wiley--VCH, expected date of publication August 2003.VCH, expected date of publication August 2003.

ISBN 3ISBN 3--527527--3068030680--33

Engel, Thomas. Engel, Thomas. ChemoinformaticsChemoinformatics: A Textbook. Wiley: A Textbook. Wiley--VCH, expected date of publication: August 2003.VCH, expected date of publication: August 2003.

ISBN 3ISBN 3--527527--3068130681--11

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Reference WorksReference Works

Encyclopedia of Computational Chemistry,Encyclopedia of Computational Chemistry, SchleyerSchleyer, P. , P. von R.;von R.; AllingerAllinger, N.L.; Clark, T.;, N.L.; Clark, T.; GasteigerGasteiger, J.;, J.; KollmanKollman, , P.A.; Schaefer, H.F.;P.A.; Schaefer, H.F.; ShreinerShreiner, P.R. (Eds.). 5 v. Wiley,, P.R. (Eds.). 5 v. Wiley,ChichesterChichester, 1998., 1998.

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

Paris, Greg. Bibliography: Chemical Information Paris, Greg. Bibliography: Chemical Information Retrieval and 3D Searching. Retrieval and 3D Searching. http://http://panizzipanizzi..shefshef.ac..ac.ukuk//cisrgcisrg/links//links/grepgrep//chemDBchemDB.4.html .4.html

SIRChSIRCh: Chemical Informatics Home Page at Indiana : Chemical Informatics Home Page at Indiana University University http://www.http://www.indianaindiana..eduedu/~/~cheminfocheminfo/informatics//informatics/cinformhomecinformhome.html.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. “Brown, F.K. “ChemoinformaticsChemoinformatics, what it is and how does it impact drug , what it is and how does it impact drug discovery.” Annual Reports in Medicinal Chemistry, 1998, 33, 37discovery.” Annual Reports in Medicinal Chemistry, 1998, 33, 3755--384.384.Glen, Robert. “Developing tools and standards in molecular inforGlen, Robert. “Developing tools and standards in molecular informatics.” matics.” Chemical Communications, 2002, (23), 2745Chemical Communications, 2002, (23), 2745--2747.2747.HannHann, Mike; Green, Richard. “, Mike; Green, Richard. “ChemoinformaticsChemoinformatics——a new name for an old a new name for an old problem?” Current Opinion in Chemical Biology, 1979, 3, 379problem?” Current Opinion in Chemical Biology, 1979, 3, 379--383.383.Lipinski, C.A.; Lombardo, F.; Lipinski, C.A.; Lombardo, F.; DominyDominy, B.W.; Feeney, P.J. “Experimental and , B.W.; Feeney, P.J. “Experimental and computational approaches to estimate the solubility and permeabicomputational approaches to estimate the solubility and permeability in drug lity in drug discovery and development settings. Advanced Drug Delivery Revidiscovery and development settings. Advanced Drug Delivery Reviews, ews, 1997, 23, 31997, 23, 3--15.15.RossoRosso, Eugene. “Chemistry plans a structural overhaul.” Nature , Eugene. “Chemistry plans a structural overhaul.” Nature ((NaturejobsNaturejobs) 12 September 2002, 419(6903). ) 12 September 2002, 419(6903).

http://www.nature.com/http://www.nature.com/naturejobsnaturejobs//careersandrecruitmentcareersandrecruitment/2002.html /2002.html

Rothman, L. David. “Information management for research in the Rothman, L. David. “Information management for research in the chemical chemical industry.” Abstracts of Papers, 223rd ACS National Meeting, Oindustry.” Abstracts of Papers, 223rd ACS National Meeting, Orlando, FL, rlando, FL, United States, April 7United States, April 7--11, 2002 (2002), CINF11, 2002 (2002), CINF--044.044.Smith, Chris. “Smith, Chris. “CheminformaticsCheminformatics: Redefining the crucible.” The Scientist, : Redefining the crucible.” The Scientist, 2002, 16(8), 40.2002, 16(8), 40.

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