twenty five years of progress in cheminformatics - wendy warr

Wendy Warr & Associates

Twenty Five Years of Progress in Twenty Five Years of Progress in CheminformaticsCheminformatics

Dr. Wendy A. WarrDr. Wendy A. Warrhttp://http://www.warr.comwww.warr.com


JCIM

J. Chem. Inf. Comput. Sci.(JCICS)is nowJ. Chem. Inf. Model. (JCIM)


The ChemistThe ChemistReaderReaderAuthorAuthor

ReviewerReviewer EditorEditor


Our AuthorsOur Authors


SciFinderSciFinderGasteigerGasteiger


ACS Award for Computers in Chemical ACS Award for Computers in Chemical and Pharmaceutical Researchand Pharmaceutical Research

1986 Raymond E. 1986 Raymond E. DessyDessy1987 W. Todd 1987 W. Todd WipkeWipke1988 W.A. Goddard III1988 W.A. Goddard III1989 Christie G. 1989 Christie G. EnkeEnke1990 Peter C. 1990 Peter C. JursJurs1991 John A. 1991 John A. PoplePople1992 Ernest R. Davidson1992 Ernest R. Davidson1993 W. Clark Still1993 W. Clark Still1994 Michael J.S. Dewar1994 Michael J.S. Dewar1995 Peter A. 1995 Peter A. KollmanKollman1996 Norman L. 1996 Norman L. Allinger

1997 Harold A. 1997 Harold A. ScheragaScheraga1998 William L. Jorgensen1998 William L. Jorgensen1999 Corwin H. 1999 Corwin H. HanschHansch2000 Donald G. 2000 Donald G. TruhlarTruhlar2001 Martin 2001 Martin KarplusKarplus2002 Irwin D. Kuntz2002 Irwin D. Kuntz2003 Kendall N. 2003 Kendall N. HoukHouk2004 W. Graham Richards2004 W. Graham Richards2005 Peter Willett2005 Peter Willett2006 Johann 2006 Johann GasteigerGasteiger

Allinger


ACS Division of Chemical InformationACS Division of Chemical InformationHerman Herman SkolnikSkolnik AwardAward

Herman Herman SkolnikSkolnik (1976)(1976)Eugene Garfield (1977)Eugene Garfield (1977)Fred A. Tate (1978)Fred A. Tate (1978)William J. William J. WiswesserWiswesser (1979)(1979)Ben H. Weil (1981)Ben H. Weil (1981)*Robert *Robert FugmannFugmann (1982)(1982)Russell J. Rowlett, Jr. (1983)Russell J. Rowlett, Jr. (1983)MontaguMontagu HyamsHyams (1984)(1984)Dale B. Baker (1986)Dale B. Baker (1986)William William TheilheimerTheilheimer (1987)(1987)David R. David R. LideLide, Jr. (1988), Jr. (1988)Michael F. Lynch (1989)Michael F. Lynch (1989)Stuart A. Stuart A. MarsonMarson (1989)(1989)*Ernst Meyer (1990)*Ernst Meyer (1990)W. Todd W. Todd WipkeWipke (1991)(1991)JaquesJaques--Emile Dubois (1992)

Peter Willett (1993)Peter Willett (1993)AlexandruAlexandru T. T. BalabanBalaban (1994)(1994)**ReinerReiner LuckenbachLuckenbach (1995)(1995)*Clemens *Clemens JochumJochum (1995)(1995)Milan Milan RandicRandic (1996)(1996)*Johann *Johann GasteigerGasteiger (1997)(1997)Gary Wiggins (1998)Gary Wiggins (1998)Stuart Stuart KabackKaback (1999)(1999)Stephen R. Heller (2000)Stephen R. Heller (2000)G.W.A. (Bill) Milne (2000)G.W.A. (Bill) Milne (2000)GuenterGuenter GretheGrethe (2001)(2001)Peter Norton (2002)Peter Norton (2002)Frank Allen (2003)Frank Allen (2003)Peter Johnson (2004)Peter Johnson (2004)LorrinLorrin Garson (2005)Garson (2005)Hugo Hugo KubinyiKubinyi (2006)(2006)Emile Dubois (1992)


ACS Division of Chemical InformationACS Division of Chemical InformationHerman Herman SkolnikSkolnik AwardAward

•• Robert Robert FugmannFugmann (1982)(1982)•• Ernst Meyer (1990)Ernst Meyer (1990)•• ReinerReiner LuckenbachLuckenbach (1995)(1995)•• Clemens Clemens JochumJochum (1995)(1995)•• Johann Johann GasteigerGasteiger (1997)(1997)

•• GuenterGuenter GretheGrethe (2001)(2001)•• Hugo Hugo KubinyiKubinyi (2006)(2006)


WiswesserWiswesser Line NotationLine Notation

NO2

OSO2

N

Cl

T6NJ NWB C DOSWR G


CROSSBOWCROSSBOWCComputerizedomputerizedRRetrieval ofetrieval ofSStructuretructureSSBBasedasedOOnnWWiswesseriswesser


Structure RepresentationStructure Representation

•• WeiningerWeininger, D., D. SMILES, a chemical language SMILES, a chemical language and information system. 1. Introduction to and information system. 1. Introduction to methodology and encoding rules. methodology and encoding rules. J. Chem. J. Chem. Inf. Inf. ComputComput. . SciSci.. 19881988, , 2828, 31, 31--36.36.

•• WeiningerWeininger, D.; , D.; WeiningerWeininger, A.; , A.; WeiningerWeininger, J. L. , J. L. SMILES. 2. Algorithm for generation of SMILES. 2. Algorithm for generation of unique SMILES notation. unique SMILES notation. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci.. 19891989, , 2929, 97, 97--101.101.



•• Morgan, H. L. The generation of a unique Morgan, H. L. The generation of a unique machine description for chemical structures machine description for chemical structures --a technique developed at Chemical Abstracts a technique developed at Chemical Abstracts Service. Service. J. Chem. Doc.J. Chem. Doc. 19651965, , 55, 107, 107--113.113.

•• WipkeWipke, W. T.;, W. T.; DyottDyott, T. M. , T. M. StereochemicallyStereochemicallyunique naming algorithm.unique naming algorithm. J. Am. Chem. Soc.J. Am. Chem. Soc.19741974, , 9696(15), 4834(15), 4834--4842.4842.



•• Canonical numbering for Canonical numbering for InChIInChI: : modified from McKay, B. D. Practical modified from McKay, B. D. Practical graph isomorphism. graph isomorphism. CongressusCongressusNumerantiumNumerantium 19811981, , 3030, 45, 45––87.87.


Substructure SearchingSubstructure Searching

•• NIH/EPA Chemical Information SystemNIH/EPA Chemical Information System•• DARCDARC•• CAS ONLINECAS ONLINE•• MACCS/ISISMACCS/ISIS


MeyerMeyer’’s Formula Reading s Formula Reading MachineMachine


ImlacImlac TerminalTerminal


VT640 TerminalVT640 Terminal


1984 VAX 11/7501984 VAX 11/750

•• Clock speed 6 MHzClock speed 6 MHz•• 2 Mb memory2 Mb memory•• 134 Mb fixed disk134 Mb fixed disk•• Two 67 Mb exchangeable disk drivesTwo 67 Mb exchangeable disk drives•• Shared peripheralsShared peripherals•• ££100,000 (1984 price)100,000 (1984 price)


WWindowsindows

IIconscons

MMiceice

PPointersointers


MicrocomputersMicrocomputers


IvarIvar UgiUgi1930 1930 -- 20052005


CAOSCAOS

•• Corey, E.J.; Corey, E.J.; WipkeWipke, W.T. Computer, W.T. Computer--assisted Design assisted Design of Complex Organic Syntheses. of Complex Organic Syntheses. ScienceScience, , 19691969, , 166 166 ((39023902)), , 178178--192.192.

•• DugundjiDugundji, J.; , J.; UgiUgi, I. Algebraic Model of , I. Algebraic Model of Constitutional Chemistry as a basis for Chemical Constitutional Chemistry as a basis for Chemical Computer Programs. Computer Programs. Top. Top. CurrCurr. Chem.. Chem. 19731973, , 3939, , 1919--64.64.

•• Bauer, J.; Bauer, J.; HergesHerges, R.; , R.; FontainFontain, E.; , E.; UgiUgi, I. IGOR and , I. IGOR and Computer Assisted Innovation in Chemistry. Computer Assisted Innovation in Chemistry. ChimiaChimia, , 1985, 39, 451985, 39, 45--53.53.


Reaction ProgramsReaction Programs

•• Reaction retrievalReaction retrieval•• Synthetic analysisSynthetic analysis

–– Synthesis designSynthesis design–– Reaction predictionReaction prediction–– Mechanism elucidationMechanism elucidation


Reaction RetrievalReaction Retrieval

•• REACCS/ISISREACCS/ISIS•• ORACORAC•• CASREACTCASREACT


Synthetic AnalysisSynthetic Analysis

•• LogicLogic--orientedoriented–– IGORIGOR–– EROS EROS –– SYNGENSYNGEN–– CAMEOCAMEO–– WODCAWODCA

•• InformationInformation--orientedoriented–– LHASALHASA–– SECS/CASPSECS/CASP


Reaction ClassificationReaction Classification

InfoChemInfoChem Classification AlgorithmClassification Algorithm

CLASSIFYCLASSIFY


Cambridge Structural DatabaseCambridge Structural Database

•• Allen, F. H. The Cambridge Structural Allen, F. H. The Cambridge Structural Database: a quarter of a million structures Database: a quarter of a million structures and rising. and rising. ActaActa CrystCryst. Section B. Section B 20022002, , 5858, , 380380--388.388.

•• Allen, F. H.; Davies, J. E.; Allen, F. H.; Davies, J. E.; GalloyGalloy, J. J.; , J. J.; Johnson, O.; Kennard, O.; Johnson, O.; Kennard, O.; MacraeMacrae, C. F.; , C. F.; Mitchell, E. M.; Mitchell, G. F.; Smith, J. M.; Mitchell, E. M.; Mitchell, G. F.; Smith, J. M.; Watson, D. G. The development of versions 3 Watson, D. G. The development of versions 3 and 4 of the Cambridge Structural Database and 4 of the Cambridge Structural Database System. System. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci.. 19911991, , 31,31,187187--204.204.


3D Structures3D Structures

•• Pearlman, R. S. Rapid generation of high quality Pearlman, R. S. Rapid generation of high quality approximate 3D molecular structures. approximate 3D molecular structures. Chemical Chemical Design Automation NewsDesign Automation News, , 19871987, , 2,2, 1, 51, 5--7.7.

•• Hiller, C.; Hiller, C.; GasteigerGasteiger, J. , J. EinEin automatisierterautomatisierterMolekMoleküülbaukastenlbaukasten. In . In SoftwareSoftware--EntwicklungEntwicklung in in derderChemieChemie, , GasteigerGasteiger, J., Ed.; Springer: Berlin, 1987; , J., Ed.; Springer: Berlin, 1987; Vol. 1; pp. 53Vol. 1; pp. 53--66.66.

•• GasteigerGasteiger, J.; Rudolph, C.; , J.; Rudolph, C.; SadowskiSadowski, J., J.Automatic generation of 3D atomic coordinates for Automatic generation of 3D atomic coordinates for organic molecules. organic molecules. Tetrahedron Computer Tetrahedron Computer MethodologyMethodology 19901990, , 33, 537, 537--547. 547.


GasteigerGasteiger Most CitedMost Cited

SadowskiSadowski, J.; , J.; GasteigerGasteiger, J.; , J.; KlebeKlebe, G. , G. Comparison of Automatic ThreeComparison of Automatic Three--Dimensional Model Builders Using 639 Dimensional Model Builders Using 639 XX--ray Structuresray Structures. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci.. 19941994, , 3434, 1000, 1000--1008. 1008.


3D Searching3D Searching•• Jakes, S.E.; Willett, P. Jakes, S.E.; Willett, P. PharmacophoricPharmacophoric pattern pattern

matching in files of 3D chemical structures: selection matching in files of 3D chemical structures: selection of interof inter--atomic distance screens. atomic distance screens. J. Mol. Graph.J. Mol. Graph. 19861986, , 44, 12, 12-- 20.20.

•• CringeanCringean, J.K.; , J.K.; PepperrellPepperrell, C.A.; , C.A.; PoirrettePoirrette, A.R.; , A.R.; Willett, P. Selection of screens for threeWillett, P. Selection of screens for three--dimensional dimensional substructure searching. substructure searching. Tetrahedron Computer Tetrahedron Computer MethodologyMethodology 19901990, , 33, 37, 37--46.46.

•• BrintBrint, A. T.; Willett, P. , A. T.; Willett, P. PharmacophoricPharmacophoric Pattern Pattern Matching in Files of 3D Chemical Structures: Matching in Files of 3D Chemical Structures: Comparison of Geometric Searching Algorithms. Comparison of Geometric Searching Algorithms. J. J. Mol. Graph.Mol. Graph. 19871987, , 55, 49, 49--56.56.


3D Searching3D Searching

•• Martin, Y. C.; Danaher, E. B.; May, C. S.; Martin, Y. C.; Danaher, E. B.; May, C. S.; WeiningerWeininger, D. , D. MENTHOR, a database system for the storage and MENTHOR, a database system for the storage and retrieval of threeretrieval of three--dimensional molecular structures and dimensional molecular structures and associated data searchable by associated data searchable by substructuralsubstructural, biologic, , biologic, physical, or geometric properties. physical, or geometric properties. J. J. ComputComput..--Aided Mol. Aided Mol. DesignDesign 19881988, , 22((11), 15), 15--29.29.

•• Van Van DrieDrie, J. H.; , J. H.; WeiningerWeininger, D.; Martin, Y. C. ALADDIN: , D.; Martin, Y. C. ALADDIN: an integrated tool for computeran integrated tool for computer--assisted molecular assisted molecular design and design and pharmacophorepharmacophore recognition from geometric, recognition from geometric, stericsteric, and substructure searching of three, and substructure searching of three--dimensional dimensional molecular structures. molecular structures. J. J. ComputComput..--Aided Mol. DesignAided Mol. Design19891989, , 33((33), 225), 225--251.251.


Molecules TwistMolecules Twist


O

OH

NH2

N

O

N

N OO

Br

N

O

N

O

NN

O

O

O

O

OO MolecularMolecular

DiversityDiversity

NHO

N

O

R1

O

O

O

O O

O

O

O

P

O

O


SelectionSelection

1010180180 possible drugs...10possible drugs...101818 likely drugs...likely drugs...101077 known compounds...10known compounds...1066 commerciallycommerciallyavailable...10available...106 6 in corporate databases...in corporate databases...101044 in drug databases...10in drug databases...1033 commercial commercial drugs...drugs...

101022 profitable drugsprofitable drugs


Library DesignLibrary Design

•• Random screening is too expensiveRandom screening is too expensive•• Its hit rate is lowIts hit rate is low•• False positives may be a problemFalse positives may be a problem•• HTS consumes expensive compoundsHTS consumes expensive compounds•• There are too many possible There are too many possible

compoundscompounds•• How to choose those most likely to be How to choose those most likely to be

hits?hits?


Selecting Diverse SubsetsSelecting Diverse Subsets

•• ClusteringClustering•• DissimilarityDissimilarity--based selectionbased selection•• Partitioning/cellPartitioning/cell--based approachesbased approaches•• OptimizationOptimization--based methodsbased methods


Measuring DiversityMeasuring Diversity

Martin, E. J.; Martin, E. J.; BlaneyBlaney, J. M.; , J. M.; SianiSiani, M. A.; , M. A.; SpellmeyerSpellmeyer, D. C.; Wong, A. K.; Moos, , D. C.; Wong, A. K.; Moos, W. H. W. H. Measuring diversity: experimental Measuring diversity: experimental design of combinatorial libraries for drug design of combinatorial libraries for drug discovery.discovery. J. Med. Chem.J. Med. Chem. 19951995, , 3838, , 14311431--1436.1436.


DiversityDiversity

•• Brown, R. D.; Martin, Y. C. Use of structureBrown, R. D.; Martin, Y. C. Use of structure--activity data to compare structureactivity data to compare structure--based based clustering methods and descriptors for use in clustering methods and descriptors for use in compound selection. compound selection. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci.. 19961996, , 3636, 572 , 572 --584.584.

•• Brown, R. D.; Martin, Y. C. The information Brown, R. D.; Martin, Y. C. The information content of 2D and 3D structural descriptors content of 2D and 3D structural descriptors relevant to relevant to ligandligand--receptor binding. receptor binding. J. Chem. J. Chem. Inf. Inf. ComputComput. . SciSci.., , 3737 (1), 1 (1), 1 --9, 1997.9, 1997.


ProductProduct--based orbased orReagentReagent--based Designbased Design

GilletGillet, V. J.; Willett, P.; Bradshaw, J. , V. J.; Willett, P.; Bradshaw, J. The effectiveness of reactant pools for The effectiveness of reactant pools for generating structurally diverse generating structurally diverse combinatorial libraries. combinatorial libraries. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci.. 19971997, , 3737, 731, 731--740.740.


Leads and DrugsLeads and Drugs•• Lipinski, C. A.; Lombardo, F.; Lipinski, C. A.; Lombardo, F.; DominyDominy, B. W.; , B. W.;

Feeney, P. J. Experimental and Feeney, P. J. Experimental and computational approaches to estimate computational approaches to estimate solubility and permeability in drug discovery solubility and permeability in drug discovery and development settingsand development settings. Adv. Drug Delivery . Adv. Drug Delivery Rev.Rev. 19971997, , 23(123(1--3)3), 3, 3--25.25.

•• HannHann, M. H.; Leach, A. R.; Harper, G. , M. H.; Leach, A. R.; Harper, G. Molecular complexity and its impact on the Molecular complexity and its impact on the probability of finding leads for drug discovery. probability of finding leads for drug discovery. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci.. 20012001, , 4141, 856 , 856 --864. 864.


Leads and DrugsLeads and Drugs

•• OpreaOprea, T. I.; Davis, A. M.; Teague, S. J.; , T. I.; Davis, A. M.; Teague, S. J.; LeesonLeeson, P. D. Is there a difference , P. D. Is there a difference between leads and drugs? A historical between leads and drugs? A historical perspective. perspective. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci..20012001, , 4141, 1308 , 1308 --1315. 1315.

•• Teague, S. J.; Davis, A. M.; Teague, S. J.; Davis, A. M.; LeesonLeeson, P. , P. D.; D.; OpreaOprea, T. The design of , T. The design of leadlikeleadlikecombinatorial libraries. combinatorial libraries. AngewAngew. Chem., . Chem., Int. EdInt. Ed. . Engl.Engl. 19991999, , 38(24)38(24), 3743, 3743--3748.3748.


Methods for Methods for vHTSvHTS

•• Identifying drugIdentifying drug--like structureslike structures•• 2D similarity2D similarity•• 3D pharmacophores3D pharmacophores•• DockingDocking


DockingDocking•• Kuntz, I. D.; Kuntz, I. D.; BlaneyBlaney, J. M.; , J. M.; OatleyOatley, S. J.; , S. J.;

LangridgeLangridge, R.; , R.; FerrinFerrin, T. E. , T. E. J. Mol. Biol.J. Mol. Biol., , 19821982, , 161161, 269., 269.

•• ShoichetShoichet, B. K.; Kuntz, I.D. Protein docking , B. K.; Kuntz, I.D. Protein docking and and complementaritycomplementarity.. J. Mol. Biol.J. Mol. Biol. 19911991, , 221221, , 327327--46. 46.

•• ShoichetShoichet, B. K.; Stroud, R. M.; , B. K.; Stroud, R. M.; SantiSanti, D. V.; , D. V.; Kuntz, I. D.; Perry, K. M. StructureKuntz, I. D.; Perry, K. M. Structure--based based discovery of inhibitors of discovery of inhibitors of thymidylatethymidylatesynthasesynthase. . ScienceScience 1993, 1993, 259259, 1445, 1445--1450.1450.


DockingDocking•• BBööhmhm, H. J. , H. J. The development of a simple The development of a simple

empirical scoring function to estimate the empirical scoring function to estimate the binding constant for a proteinbinding constant for a protein--ligandligand complex complex of known threeof known three--dimensional structure. dimensional structure. J. J. ComputComput..--Aided Mol. Des.Aided Mol. Des. 19941994, , 88((33), ), 243243--56.56.

•• Jones, G.; Willett, P.; Glen, R. C.; Leach, A. Jones, G.; Willett, P.; Glen, R. C.; Leach, A. R.; Taylor, R. Development and validation of R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking. a genetic algorithm for flexible docking. J. J. Mol. Biol.Mol. Biol. 19971997, , 267267, 727, 727--748.748.


GOLD docking result for PDB 1FKG


Most Cited. Top TwentyMost Cited. Top Twenty•• 20.20. GilletGillet, V. J.; Willett, P.; Bradshaw, J. Identification , V. J.; Willett, P.; Bradshaw, J. Identification

of Biological Activity Profiles Using of Biological Activity Profiles Using SubstructuralSubstructuralAnalysis and Genetic Algorithms.Analysis and Genetic Algorithms. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci.. 19981998, , 3838, 165, 165--179.179.

•• 19.19. Pearlman, R. S.; Smith, K. M. Metric Validation Pearlman, R. S.; Smith, K. M. Metric Validation and the Receptorand the Receptor--Relevant Subspace ConceptRelevant Subspace Concept.. J. J. Chem. Inf. Chem. Inf. ComputComput. . SciSci. . 19991999, , 3939, 28, 28--35.35.

•• 18.18. PlattsPlatts, J. A.; , J. A.; ButinaButina, D.; Abraham, M. H.; , D.; Abraham, M. H.; HerseyHersey, , A. Estimation of Molecular Linear Free Energy A. Estimation of Molecular Linear Free Energy Relation Descriptors Using a Group Contribution Relation Descriptors Using a Group Contribution Approach. Approach. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci.. 19991999; ; 3939, 835, 835--845.845.


Most Cited. Top TwentyMost Cited. Top Twenty•• 17.17. GilletGillet, V. J.; Willett, P.; Bradshaw, J. The , V. J.; Willett, P.; Bradshaw, J. The

Effectiveness of Reactant Pools for Generating Effectiveness of Reactant Pools for Generating Structurally Diverse Combinatorial Libraries. Structurally Diverse Combinatorial Libraries. J. J. Chem. Inf. Chem. Inf. ComputComput. . SciSci.. 19971997, , 3737, 731, 731--740.740.

•• 16.16. KrygowskiKrygowski, T. M. Crystallographic Studies of , T. M. Crystallographic Studies of InterInter-- and and IntramolecularIntramolecular Interactions Reflected in Interactions Reflected in AaromaticAaromatic Character of Character of ππ--Electron Systems. Electron Systems. J. J. Chem. Inf. Chem. Inf. ComputComput. . SciSci.. 19931993, , 3333, 70, 70--78.78.

•• 1515.. HannHann, M. M.; Leach, A. R.; Harper, G. Molecular , M. M.; Leach, A. R.; Harper, G. Molecular Complexity and Its Impact on the Probability of Complexity and Its Impact on the Probability of Finding Leads for Drug Discovery. Finding Leads for Drug Discovery. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci.. 20012001,, 41,41, 856856--864.864.


Most CitedMost Cited•• 14.14. GilletGillet, V. J.; Willett, P.; Bradshaw, J. The , V. J.; Willett, P.; Bradshaw, J. The

effectiveness of reactant pools for generating effectiveness of reactant pools for generating structurally diverse combinatorial libraries. structurally diverse combinatorial libraries. J. Chem. J. Chem. Inf. Inf. ComputComput. . SciSci.. 19971997, , 3737, 731, 731--740.740.

•• 13.13. Hall, L. H.; Hall, L. H.; MohneyMohney, B; Kier, L. B. The , B; Kier, L. B. The electrotopologicalelectrotopological state: structure information at the state: structure information at the atomic level for molecular graphs. atomic level for molecular graphs. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci. . 19911991, , 31,31, 7676--82.82.

•• 12.12. Hall, L. H.;Hall, L. H.; Kier, L. B. Kier, L. B. ElectrotopologicalElectrotopological state state indices for atom types: a novel combination of indices for atom types: a novel combination of electronic, topological, and valence state information. electronic, topological, and valence state information. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci.. 19951995, , 3535, 1039, 1039--1045.1045.


Most CitedMost Cited•• 11.11. GhoseGhose, A. K.; , A. K.; CrippenCrippen, G. M. Atomic , G. M. Atomic

physicochemical parameters for threephysicochemical parameters for three--dimensionaldimensional--structurestructure--directed quantitative structuredirected quantitative structure--activity activity relationships. 2. Modeling dispersive and relationships. 2. Modeling dispersive and hydrophobic interactions. hydrophobic interactions. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci.;.;19871987, , 2727, 21, 21--35.35.

•• 10.10. CarhartCarhart, R. E.; Smith, D. H.; , R. E.; Smith, D. H.; VenkataraghavanVenkataraghavan, R. , R. Atom pairs as molecular features in structureAtom pairs as molecular features in structure--activity activity studies: definition and applications. studies: definition and applications. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci.. 19851985, , 2525, 64, 64--73.73.

•• 9.9. WesselWessel, M. D.; , M. D.; JursJurs, P. C.; , P. C.; TolanTolan, J. W.; , J. W.; MuskalMuskal, S. , S. M. Prediction of human intestinal absorption of drug M. Prediction of human intestinal absorption of drug compounds from molecular structure. compounds from molecular structure. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci.. 19981998, , 3838, 726, 726--735.735.


Most CitedMost Cited

•• 8.8. Brown, R. D.; Martin, Y. C. The information content Brown, R. D.; Martin, Y. C. The information content of 2D and 3D structural descriptors relevant to of 2D and 3D structural descriptors relevant to ligandligand--receptor binding. receptor binding. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci. . 19971997, , 3737, 1, 1--9.9.

•• 7.7. Willett, P.; Barnard, J. M.; Downs, G. M. Chemical Willett, P.; Barnard, J. M.; Downs, G. M. Chemical similarity searching. similarity searching. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci.. 19981998, , 3838, 983, 983--996.996.

•• 6.6. Rogers, D.; Rogers, D.; HopfingerHopfinger, A. J. Application of genetic , A. J. Application of genetic function approximation to quantitative structurefunction approximation to quantitative structure--activity relationships and quantitative structureactivity relationships and quantitative structure--property relationships. property relationships. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci..19941994, , 3434, 854, 854--866.866.



•• 5.5. WeiningerWeininger, D. SMILES, a chemical language and information , D. SMILES, a chemical language and information system. 1. Introduction to methodology and encoding rules. system. 1. Introduction to methodology and encoding rules. J. J. Chem. Inf. Chem. Inf. ComputComput. . SciSci.. 19881988, , 2828, 31, 31--36.36.

•• 4.4. ViswanadhanViswanadhan, V. N.; , V. N.; GhoseGhose, A. K.; , A. K.; RevankarRevankar, G. R.; Robins, , G. R.; Robins, R. K. Atomic physicochemical parameters for three dimensional R. K. Atomic physicochemical parameters for three dimensional structure directed quantitative structurestructure directed quantitative structure--activity relationships. 4. activity relationships. 4. Additional parameters for hydrophobic and dispersive Additional parameters for hydrophobic and dispersive interactions and their application for an automated superpositiointeractions and their application for an automated superposition n of certain naturally occurring nucleoside antibiotics. of certain naturally occurring nucleoside antibiotics. J. Chem. J. Chem. Inf. Inf. ComputComput. . SciSci.. 19891989, , 2929, 163, 163--172.172.

•• 3.3. Brown, R. D.; Martin, Y. C. Use of structureBrown, R. D.; Martin, Y. C. Use of structure--activity data to activity data to compare structurecompare structure--based clustering methods and descriptors for based clustering methods and descriptors for use in compound selection. use in compound selection. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci.. 19961996, , 3636, , 572572--584.584.



•• 2.2. Fletcher, D. A.; Fletcher, D. A.; McMeekingMcMeeking, R. F.; , R. F.; ParkinParkin, D. The , D. The United Kingdom chemical database service. United Kingdom chemical database service. J. Chem. J. Chem. Inf. Inf. ComputComput. . SciSci. . 19961996, , 3636, 746, 746--749.749.

•• 1.1. Allen, F. H.; Davies, J. E.; Allen, F. H.; Davies, J. E.; GalloyGalloy, J. J.; Johnson, , J. J.; Johnson, O.; Kennard, O.; O.; Kennard, O.; MacraeMacrae, C. F.; Mitchell, E. M.; , C. F.; Mitchell, E. M.; Mitchell, G. F.; Smith, J. M.; Watson, D. G. The Mitchell, G. F.; Smith, J. M.; Watson, D. G. The development of versions 3 and 4 of the Cambridge development of versions 3 and 4 of the Cambridge Structural Database System. Structural Database System. J. Chem. Inf. J. Chem. Inf. ComputComput. . SciSci.. 19911991, , 31,31, 187187--204.204.


AcknowledgmentsAcknowledgments

•• Chemical Abstracts ServiceChemical Abstracts Service•• Eric Shively, CASEric Shively, CAS•• Michael LynchMichael Lynch


The Next 25 Years?The Next 25 Years?


Fearless predictionsFearless predictions……

““Where a calculator on the Where a calculator on the EniacEniac is is equipped with 18,000 vacuum tubes and equipped with 18,000 vacuum tubes and weighs 30 tons, computers in the future weighs 30 tons, computers in the future may have only 1,000 vacuum tubes and may have only 1,000 vacuum tubes and perhaps weigh 1.5 tons.perhaps weigh 1.5 tons.””

Popular Mechanics, Popular Mechanics, MarchMarch 19491949


Basic Principle of ForecastingBasic Principle of Forecasting

““Give them a number or give them a date,Give them a number or give them a date,but never both.but never both.””

Edgar FiedlerEdgar Fiedler


Technology Adoption CycleTechnology Adoption Cycle


Information OverloadInformation Overload

•• The LordThe Lord’’s Prayer uses 56 wordss Prayer uses 56 words•• The Ten Commandments, 297 wordsThe Ten Commandments, 297 words•• The American Declaration of The American Declaration of

Independence, 300 wordsIndependence, 300 words•• The EEC Directive on the import of The EEC Directive on the import of

caramel and caramel products uses caramel and caramel products uses 26,911 words26,911 words


A Mobile CAS ServiceA Mobile CAS Service


New Infrastructures, MiddlewareNew Infrastructures, Middleware

•• ee--ScienceScience•• CyberinfrastructureCyberinfrastructure•• eSciDoceSciDoc


““Here we sit side by side with thoseHere we sit side by side with thoseon whose shoulders we standon whose shoulders we stand””

Michael Lynch, 2002Michael Lynch, 2002

twenty five years of progress in cheminformatics - wendy warr

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