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C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Chemoinformatics in Europe:Achievements and Perspectives
Johann GasteigerComputer-Chemie-Centrum
University of Erlangen-NürnbergD-91052 Erlangen, Germany
www2.chemie.uni-erlangen.de/
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Overview
• chemoinformatics - definition
• the bright past
• the grim presence
• the bright future ?
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Synthesis of Properties
The most fundamental and lasting objective of synthesis is not
production of new compoundsbut
production of properties
George S. HammondNorris Award Lecture, 1968
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
What structure do I need for a certain property?structure-activity relationships
How do I make this structure?synthesis design
What is the product of my reaction?reaction predictionstructure elucidation
Fundamental Questions in Chemistry
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Chemoinformatics - Why?
• complex relationshipsstructure - biological activitychemical reactivity
• amount of informationmany millions of compounds and reactionsmany millions of publications
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
From Data to Knowledge
know-ledge
information
data
generalization
context
measurementcalculation
deductivelearning
inductivelearning
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Chemoinformatics: Definition
The application of
informatics methods
to solve
chemical problems
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Application Areas for Chemoinformatics
• drug design
• analytical chemistry
• chemical engineering
• inorganic chemistry
• medicinal chemistry
• organic chemistry
• physical chemistry
• theoretical chemistry
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
chemicalstructure
physicalproperty
chemicalproperty biological
property
starting materials
synthesisplanning
reactionpredictionstructure
elucidation
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
The Scope of Chemoinformatrics
• structure representation and searching
• data analysis and chemometrics
• molecular modeling
• spectra analysis and structure elucidation
• reaction representation and searching
• reaction modeling and synthesis design
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
• structure representation1965, Morgan
• structure elucidation1965, Sasaki, Munk, DENDRAL
• synthesis design1970, Corey & Wipke, Ugi, Gelernter, Hendrickson
• molecular modeling1970, Langridge, Marshall
• data analysis / chemometrics1970, Kowalski, Wold
Chemoinformatics – An Old Discipline
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
• data storage and retrieval
• property prediction
• drug design
• synthesis design
• spectra analysis and prediction
Common Topics: Structure Representation
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Common Topics: Data Analysis Methods
• property prediction
• drug design
• analytical chemistry
• spectra analysis and prediction
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
gene drugprotein lead
Bioinformatics Chemoinformatics
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Biochemical Pathways
/slides/Biochemical_Pathways/Folien/CCC/roche_2.ppt© Gasteiger et al.C3
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al. /slides/Biochemical_Pathways/Folien/CCC/gcb00.ppt© Gasteiger et al.C3
What is a Chemical Reaction?
+
the bioinformaticianan event influenced by a gene, a protein
the computer scientista context sensitive graph rewriting rule
the chemistan event breaking and making bonds
EC - Nr.: 4.1.3.7COOHC
CH2
O
COOH
CH3 CO
S CoA
COOH
CH2
C
CH2
COOHHO
COOH
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Glucose6-phosphate
NADP+
NADPH H+
6-Phospho-gluconolactone
H2O6-Phospho-gluconate
Ribulose5-phosphate
CO2
Xylulose5-phosphate
Ribose5-phosphate
Glyceraldehyde3-phosphate
Sedoheptulose7-phosphate
Erythrose4-phosphate
Fructose6-phosphate
H+NADP+NADPH
1
3
45
6
2
5
9
24
7
8
10 11
14
Glyceraldehyde3-phosphate
15
1
23
45
67
8
10
12
12 13
14
1512
5[r10] 5[r12] 10[r14] 10[r1] 10[r2] 10[r3] 8[r4] 3[r6] 3[r8]
2[c13] 20[c2] 10[c6] 1[c8] ---> 20[c4] 20[c5] 10[c9] 3[c12]
maximize NADPH production
Pathway Searching
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Handbook of Chemoinformatics
J. Gasteiger (Editor)
65 authors73 contributions
4 volumes1900 pages
Wiley-VCH, Weinheim(August 2003)
From Data to Knowledge
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Textbooks on Chemoinformatics
• V. Gillet, A. Leach
• J. Gasteiger, T. Engel
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Major Contributions from Europe
• structure representation• data analysis methods• databases• research centers• funding• industry• teaching
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Structure Representation (Europe)
European industry: BASF, Hoechst, ICI, Thomae,BASIC, IDC
Sheffield: M. Lynch, P. Willett
Munich: I. Ugi, J. Gasteiger, C. Jochum
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Data Analysis Methods (Europe)
PLS: S. Wold
Self-organizing neural network: Kohonen
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Databases (Europe)
Cambridge CSD
Inorganic Structures Database
Beilstein
Gmelin
ChemInformRX
SpecInfo
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Institutions and Research Centers (Europe)
FIZ Karlsruhe, D
FIZ Chemie, D
CAOS/CAMM Center, Nijmegen, NL
Computer-Chemie-Centrum, Erlangen, D
Center for Molecular Informatics, Cambridge, UK
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Funding (Germany)Fachinformationsprogramm 1981 - 1994German Federal Minister of Research and Technology (BMFT)(Dr. Riesenhuber, chemist !)institutions
FIZ KarlsruheFIZ Chemie
databasesBeilsteinGmelinChemInformRXSpecInfo
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Industry (Europe)
• early work on databases
• positions in chemoinformatics
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Teaching (Europe)
Sheffield
UMIST
Strasbourg
Erlangen
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Databases (Europe)
Cambridge CSD
Inorganic Structures Database
Beilstein -
Gmelin -
ChemInformRX -
SpecInfo
however:
distributed by
MDL Elsevier
expensive;
academia cut off?
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Institutions and Research Centers (Europe)
FIZ Karlsruhe, D
FIZ Chemie, D
CAOS/CAMM Center, Nijmegen, NL
Computer-Chemie-Centrum, Erlangen, D
Center for Molecular Informatics, Cambridge, UK
however:no research
no research
no long-term commitmentsuccessor to J. Gasteiger ?no long-term commitment
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Funding (Germany)Fachinformationsprogramm 1981 - 1994German Federal Minister of Research and Technology (BMFT)(Dr. Riesenhuber, chemist !)institutions
FIZ KarlsruheFIZ Chemie
databasesBeilsteinGmelinChemInformRXSpecInfo
however:
now all BMBF projects go into
bioinformatics
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Industry
• early work on databases
• positions in chemoinformatics
however:• hardly any in-house work done anymore• mergers lead to elimination of positions
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Teaching (Europe)
Sheffield
UMIST
Strasbourg
Erlangen
however:
discontinued?
only for Molecular Science students
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Funding (Europe)
6th Framework program of the European Union:
several programs for Bioinformatics
however: no mention of Chemoinformatics!
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
What Can be Done?
• conferences
• teaching
• cooperation academia – industry
• new application areas
• funding
• organization
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Germany Chemical Society (GDCh)
Division “Chemical Information” changed to“Chemical-Information-Computer (CIC)” in 1987
Workshop:Software Development in Chemistry 1986-2004German Conference on Chemoinformatics 2005
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Teaching
• define curriculum in chemoinformatics
• what contents of chemoinformatics have to go into regular chemistry curricula
Round Table + Committee
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Bioinformatics in Germany
Fachgruppe 4 der Gesellschaft für Informatik(Division 4 of the Society for Informatics)
• definiton of a curriculum on Bioinformatics in 1990
• was then put on the web
all positions in bioinformatics at German universities were given to computer scientists
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Application Areas for Chemoinformatics
• drug design
• analytical chemistry
• chemical engineering
• inorganic chemistry
• medicinal chemistry
• organic chemistry
• physical chemistry
• theoretical chemistry
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Cooperation Industry - Academia
• industry: generate data
• academia: develop methods
provide academia access to data
C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.
Funding
• increase awareness for importance of Chemoinformatics
• go into committees