1. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. Chemoinformatics in Europe: Achievements and Perspectives Johann Gasteiger Computer-Chemie-Centrum University of Erlangen-Nürnberg D-91052 Erlangen, Germany www2.chemie.uni-erlangen.de/

2. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. Overview chemoinformatics - definition the bright past the grim presence the bright future ?

3. C3C3 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 compounds but production of properties George S. Hammond Norris Award Lecture, 1968

4. C3C3 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 prediction structure elucidation Fundamental Questions in Chemistry

5. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. Chemoinformatics - Why? complex relationships structure - biological activity chemical reactivity amount of information many millions of compounds and reactions many millions of publications

6. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. From Data to Knowledge know- ledge information data generalization context measurement calculation deductive learning inductive learning

7. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. Chemoinformatics: Definition The application of informatics methods to solve chemical problems

8. C3C3 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

9. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. chemical structure physical property chemical property biological property starting materials synthesis planning reaction prediction structure elucidation

10. C3C3 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

11. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. 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

12. C3C3 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

13. C3C3 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

14. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. gene drug protein lead Bioinformatics Chemoinformatics

15. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. Biochemical Pathways /slides/Biochemical_Pathways/Folien/CCC/roche_2.ppt © Gasteiger et al. C3C3

16. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. /slides/Biochemical_Pathways/Folien/CCC/gcb00.ppt © Gasteiger et al. C3C3 What is a Chemical Reaction? the bioinformatician an event influenced by a gene, a protein the computer scientist a context sensitive graph rewriting rule the chemist an event breaking and making bonds

17. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. Glucose 6-phosphate NADP + NADPHH+H+ 6-Phospho -gluconolactone H2OH2O 6-Phospho -gluconate Ribulose 5-phosphate CO 2 Xylulose 5-phosphate Ribose 5-phosphate Glyceraldehyde 3-phosphate Sedoheptulose 7-phosphate Erythrose 4-phosphate Fructose 6-phosphate H+H+ NADP + NADPH 1 3 4 5 6 2 5 9 24 7 8 1011 14 Glyceraldehyde 3-phosphate 15 1 2 3 4 5 6 7 8 10 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

18. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. Handbook of Chemoinformatics J. Gasteiger (Editor) 65 authors 73 contributions 4 volumes 1900 pages Wiley-VCH, Weinheim (August 2003) From Data to Knowledge

19. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. Textbooks on Chemoinformatics V. Gillet, A. Leach J. Gasteiger, T. Engel

20. C3C3 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

21. C3C3 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

22. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. Data Analysis Methods (Europe) PLS: S. Wold Self-organizing neural network: Kohonen

23. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. Databases (Europe) Cambridge CSD Inorganic Structures Database Beilstein Gmelin ChemInformRX SpecInfo

24. C3C3 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

25. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. 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

26. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. Industry (Europe) early work on databases positions in chemoinformatics

27. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. Teaching (Europe) Sheffield UMIST Strasbourg Erlangen

28. C3C3 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?

29. C3C3 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 long-term commitment successor to J. Gasteiger ? no long-term commitment

30. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. 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

31. C3C3 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

32. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. Teaching (Europe) Sheffield UMIST Strasbourg Erlangen however: discontinued? only for Molecular Science students

33. C3C3 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!

34. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. What Can be Done? conferences teaching cooperation academia – industry new application areas funding organization

35. C3C3 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 1986-2004 German Conference on Chemoinformatics 2005

36. C3C3 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

37. C3C3 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

38. C3C3 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

39. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. Cooperation Industry - Academia industry: generate data academia: develop methods provide academia access to data

40. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. Funding increase awareness for importance of Chemoinformatics go into committees

41. C3C3 Introduction into CI; SS 03/1st lecture © Gasteiger et al. Get Organized! Chemometrics Society QSAR Society FECS Working Party: Computational Chemistry Chemoinformatics Society