C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. Chemoinformatics in Europe:...

C3 Introduction into CI; SS 03/1st lecture© Gasteiger et al.

Chemoinformatics in Europe:Achievements and Perspectives

Johann GasteigerComputer-Chemie-Centrum

University of Erlangen-Nürnberg

D-91052 Erlangen, Germany

www2.chemie.uni-erlangen.de/


Overview

• chemoinformatics - definition

• the bright past

• the grim presence

• the bright future ?


Synthesis of Properties

The most fundamental and lasting objective of synthesis is not

production of new compounds

but

production of properties

George S. HammondNorris Award Lecture, 1968


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


Chemoinformatics - Why?

• complex relationships

structure - biological activity

chemical reactivity

• amount of information

many millions of compounds and reactions

many millions of publications


From Data to Knowledge

know-ledge

information

data

generalization

context

measurementcalculation

deductivelearning

inductivelearning


Chemoinformatics: Definition

The application of

informatics methods

to solve

chemical problems


Application Areas for Chemoinformatics

• drug design

• analytical chemistry

• chemical engineering

• inorganic chemistry

• medicinal chemistry

• organic chemistry

• physical chemistry

• theoretical chemistry


chemicalstructure

physicalproperty

chemicalproperty biological

property

starting materials

synthesisplanning

reactionpredictionstructure

elucidation


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


• structure representation

1965, Morgan• structure elucidation

1965, Sasaki, Munk, DENDRAL• synthesis design

1970, Corey & Wipke, Ugi, Gelernter, Hendrickson• molecular modeling

1970, Langridge, Marshall• data analysis / chemometrics

1970, Kowalski, Wold

Chemoinformatics – An Old Discipline


• data storage and retrieval

• property prediction

• drug design

• synthesis design

• spectra analysis and prediction

Common Topics: Structure Representation


Common Topics: Data Analysis Methods

• property prediction

• drug design


• spectra analysis and prediction


gene drugprotein lead

Bioinformatics Chemoinformatics


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.: 4.1.3.7COOH

C

CH2

O

COOH

CH3 CO

S CoA

COOH

CH2

C

CH2

COOHHO

COOH


Glucose6-phosphate

NADP+

NADPH H+

6-Phospho-gluconolactone

H2O

6-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


Handbook of Chemoinformatics

J. Gasteiger (Editor)

65 authors73 contributions

4 volumes1900 pages

Wiley-VCH, Weinheim(August 2003)

From Data to Knowledge


Textbooks on Chemoinformatics

• V. Gillet, A. Leach

• J. Gasteiger, T. Engel


Major Contributions from Europe

• structure representation• data analysis methods• databases• research centers• funding• industry• teaching


Structure Representation (Europe)

European industry: BASF, Hoechst, ICI, Thomae,

BASIC, IDC

Sheffield: M. Lynch, P. Willett

Munich: I. Ugi, J. Gasteiger, C. Jochum


Data Analysis Methods (Europe)

PLS: S. Wold

Self-organizing neural network: Kohonen


Databases (Europe)

Cambridge CSD

Inorganic Structures Database

Beilstein

Gmelin

ChemInformRX

SpecInfo


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


Funding (Germany)

Fachinformationsprogramm 1981 - 1994

German Federal Minister of Research and Technology (BMFT)

(Dr. Riesenhuber, chemist !)

institutions

FIZ Karlsruhe

FIZ Chemie

databases

Beilstein

Gmelin

ChemInformRX

SpecInfo


Industry (Europe)

• early work on databases

• positions in chemoinformatics


Teaching (Europe)

Sheffield

UMIST

Strasbourg

Erlangen


Databases (Europe)

Cambridge CSD

Inorganic Structures Database

Beilstein -

Gmelin -

ChemInformRX -

SpecInfo

however:

distributed by

MDL Elsevier

expensive;

academia cut off?


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 commitment

successor to J. Gasteiger ?

no long-term commitment


Funding (Germany)

Fachinformationsprogramm 1981 - 1994

German Federal Minister of Research and Technology (BMFT)

(Dr. Riesenhuber, chemist !)

institutions

FIZ Karlsruhe

FIZ Chemie

databases

Beilstein

Gmelin

ChemInformRX

SpecInfo

however:

now all BMBF projects

go into

bioinformatics


Industry

• early work on databases

• positions in chemoinformatics

however:• hardly any in-house

work done anymore• mergers lead to

elimination of positions


Teaching (Europe)

Sheffield

UMIST

Strasbourg

Erlangen

however:

discontinued?

only for Molecular Science students


Funding (Europe)

6th Framework program of the European Union:

several programs for Bioinformatics

however: no mention of Chemoinformatics!


What Can be Done?

• conferences

• teaching

• cooperation academia – industry

• new application areas

• funding

• organization


Germany Chemical Society (GDCh)

Division “Chemical Information” changed to

“Chemical-Information-Computer (CIC)” in 1987

Workshop:

Software Development in Chemistry 1986-2004

German Conference on Chemoinformatics 2005


Teaching

• define curriculum in chemoinformatics

• what contents of chemoinformatics have to go into regular chemistry curricula

Round Table + Committee


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


Application Areas for Chemoinformatics

• drug design


• chemical engineering

• inorganic chemistry

• medicinal chemistry

• organic chemistry

• physical chemistry

• theoretical chemistry


Cooperation Industry - Academia

• industry: generate data

• academia: develop methods

provide academia access to data


Funding

• increase awareness for importance of Chemoinformatics

• go into committees


Get Organized!

Chemometrics Society

QSAR Society

FECS Working Party: Computational Chemistry

Chemoinformatics Society

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