1. 1 Chemoinformatics, cheminformatics, chemical informatics: What is it? Gary Wiggins and Wendie Shreve Chemistry Library Indiana University

2. 2 Abstract The terms “cheminformatics,” “chemiinformatics,” “cheminformatics,” and “chemical informatics” are all used to describe a broad array of computer techniques and applications to solve chemistry problems. We will look at the areas that comprise chemical informatics by examining the topics in existing textbooks and other secondary sources. The identified topics will be mapped to the graduate courses in the Chemical Informatics program at Indiana University

3. 3 Dmitrii Ivanovich Mendeleev, 1834-1907 Discoverer of the Periodic Table— An Early “Chemoinformatician”

4. 4 Why Mendeleev? Faced with a large amount of data, with many gaps, Mendeleev: Sought patterns where none were obvious, Sought patterns where none were obvious, Made predictions about properties of unknown chemical substances, based on observed properties of known substances, Made predictions about properties of unknown chemical substances, based on observed properties of known substances, Created a great visualization tool! Created a great visualization tool!

5. 5 The Periodic Table of the Elements by Mark Winter

6. 6 Chemical Informatics: The New “Handmaid” of Chemistry M.G. Mellon noted that Analytical Chemistry was at one time considered the handmaid of chemistry. (his Chemical Publications, 5 th ed.) Handmaid (def) – Something that is necessarily subservient or subordinate to another: Ceremony is but the handmaid of worship. (Also, Handmaiden) --Random House Unabridged Dictionary, 2 nd ed., 1993. Handmaid, maybe, but definitely not handmade!

7. 7 What is Chemical Informatics? Chemical informatics helps chemists investigate new problems and organize and analyze scientific data to develop novel compounds, materials, and processes through the application of information technology.

8. 8 Cheminformatics, etc. in the Lit, March 2000

9. 9 Cheminformatics, etc. in the Lit, 31 July 2003

10. 10 Indiana University MS in Chemical Informatics Major aspects of chemical informatics Information Acquisition: Methods for generating and collecting data empirically (experimentation) or from theory (molecular simulation) Information Acquisition: Methods for generating and collecting data empirically (experimentation) or from theory (molecular simulation) Information Management: Storage and retrieval of information Information Management: Storage and retrieval of information Information Use: Data Analysis, correlation, and application to problems in the chemical and biochemical sciences Information Use: Data Analysis, correlation, and application to problems in the chemical and biochemical sciences

11. 11 UMIST MSc in Cheminformatics “This is a modular, one-year course which provides high-level training in the handling of chemical and biochemical information, molecular modelling and other aspects of cheminformatics.”

12. 12 University of Sheffield MSc in Chemoinformatics Program “Chemoinformatics involves the application of IT to chemical data and includes topics such as chemical databases, combinatorial library design, structure- activity relationships and structure-based drug design.”

13. 13 Sheffield’s Short Course Offered for the past three summers, in 4 days, emphasizes applications in modern drug discovery Covers: 2D databases and database searching 2D databases and database searching Diversity and compound selection Diversity and compound selection Moving into 3D: experimental data sources Moving into 3D: experimental data sources Computational methods for 3D Computational methods for 3D

14. 14 Sheffield Short Course Coverage (continued): 3D databases 3D databases Combinatorial libraries Combinatorial libraries Analysis of high-throughput screening data Analysis of high-throughput screening data

15. 15 Graduate Courses in Chemical Informatics at Indiana University C571 Chemical Information Technology http://www.indiana.edu/~cheminfo/C571/571home.html C572 Molecular Modeling & Computational Chemistry http://www.indiana.edu/~cheminfo/C572/572home.html

16. 16 JCICS – Major Research Areas Chemical Information Chemical Information Text Searching Text Searching Structure and Substructure Searching Structure and Substructure Searching Databases Databases Patents Patents George W.A. Milne C571 Lecture Fall 2002

17. 17 JCICS – Major Research Areas Chemical Computation Chemical Computation Quantum Mechanics Quantum Mechanics Statistics (regression, neural nets, etc.) Statistics (regression, neural nets, etc.) QSAR, QSPR QSAR, QSPR Graph Theory Graph Theory DNA Computing DNA Computing George W.A. Milne C571 Lecture Fall 2002

18. 18 JCICS – Major Research Areas Molecular Modeling Molecular Modeling 3D Structure Generation 3D Structure Generation 3D Searching (pharmacophores) 3D Searching (pharmacophores) Docking Docking George W.A. Milne C571 Lecture Fall 2002

19. 19 JCICS – Major Research Areas Biopharmaceutical Computation Biopharmaceutical Computation Drug Design Drug Design Combinatorial Chemistry Combinatorial Chemistry Protein and Enzyme Structure Protein and Enzyme Structure Membrane Structure Membrane Structure ADME-related Research ADME-related Research George W.A. Milne C571 Lecture Fall 2002

20. 20 George W.A. Milne C571 Lecture, Fall 2002 Desirable Skills for Chemistry Grads

21. 21 Frank Brown’s Definition …the mixing of information resources to transform data into information and information into knowledge, for the intended purpose of making decisions faster in the arena of drug lead identification and optimisation. Brown, F.K. “Chemoinformatics, what it is and how does it impact drug discovery.” Annual Reports in Medicinal Chemistry, 1998, 33, 375-384. Brown, F.K. “Chemoinformatics, what it is and how does it impact drug discovery.” Annual Reports in Medicinal Chemistry, 1998, 33, 375-384.

22. 22 Application of Cheminformatics in the Drug Industry The computer is used to analyze the interactions between the drug and the receptor site and design molecules with an optimal fit. Once targets are developed, libraries of compounds are screened for activity with one or more relevant assays using High Throughput Screening.

23. 23 Application of Cheminformatics in the Drug Industry Hits are then evaluated for binding, potency, selectivity, and functional activity. Seeking to improve: Potency Potency Absorption Absorption Distribution Distribution Metabolism Metabolism Elimination Elimination

24. 24 Some Methods and Tools Structure/Activity Relationships Genetic Algorithms Statistical Tools (e.g., recursive pairing) Data Analysis Tools Visualization Hardware Developments Chemically-Aware Web Language (CML)

25. 25 CAS Indexing of a Relevant Article “The impact of informatics and computational chemistry on synthesis and screening.” Manly, Charles J.; Louise- May, Shirley; Hammer, Jack D. Drug Discovery Today (2001), 6(21), 1101- 1110. A review with 87 references

26. 26 Controlled Vocabulary Indexing of the Manly Article Chemistry High throughput screening Drug screening Bioinformatics Combinatorial chemistry Drug design Molecular modeling Pharmacokinetics Combinatorial library

27. 27 Informatics Components (per Dow Chemical Visitors) Architecture LIMSComponents of an InformaticsSystem Electronic Records Mgmt SubstanceRegistry Process Data Mgmt Integration & User Interface

28. 28 Chemical R&D vs. Pharmaceutical R&D Much smaller number of substances tested in a week Much larger number of tests to consider Answers tend to come in shades of gray rather than yes or no Targets change frequently in chemical R&D Must integrate a large variety of sources that were not designed for integration New approach to taxonomy is needed. --L. David Rothman The Dow Chemical Co.

29. 29 Characteristics of a Chemical Informatics Faculty Member Appreciates the value of algorithms Is interested in data mining, data modeling, and relational database systems Pays attention to searching issues and the literature Has compatability and commonality with bioinformatics research Is able to talk to computer scientists.

30. 30 Major Journals Journal of Chemical Information and Computer Sciences (ACS) Journal of Molecular Graphics and Modelling (Elsevier) Journal of Combinatorial Chemistry (ACS) Journal of Proteome Research (ACS) Proteomics (Wiley-VCH) Molecular and Cellular Proteomics (ASBMB) Acta Crystallographica (IUCr)

31. 31 Textbooks Leach, Andrew R.; Gillet, Valerie J. An Introduction to Chemoinformatics. Kluwer, 2003. ISBN 1-4020-1347-7 Engel, Thomas. Chemoinformatics: A Textbook. Wiley-VCH, expected date of publication: August 2003. ISBN 3-527- 30681-1

32. 32 Reference Works Encyclopedia of Computational Chemistry, Schleyer, P. von R.; Allinger, N.L.; Clark, T.; Gasteiger, J.; Kollman, P.A.; Schaefer, H.F.; Shreiner, P.R. (Eds.). 5 v. Wiley, Chichester, 1998. Gasteiger, Johann J., ed. Handbook of Chemoinformatics: From Data to Knowledge. 4 v. Wiley-VCH, expected date of publication August 2003. ISBN 3-527-30680-3 Reviews in Computational Chemistry. Wiley-VCH, 1990- Paris, Greg. Bibliography: Chemical Information Retrieval and 3D Searching. http://panizzi.shef.ac.uk/cisrg/links/grep/chemDB.4.html http://panizzi.shef.ac.uk/cisrg/links/grep/chemDB.4.html SIRCh: Chemical Informatics Home Page at Indiana University http://www.indiana.edu/~cheminfo/informatics/cinformhome.html http://www.indiana.edu/~cheminfo/informatics/cinformhome.html

33. 33 Conclusion Chemical Informatics is an evolving field with many facets. It will become increasingly important in areas of chemistry outside the drug industry. It will play an increasing role in the developing area of proteomics.

34. 34 Bibliography Brown, F.K. “Chemoinformatics, what it is and how does it impact drug discovery.” Annual Reports in Medicinal Chemistry, 1998, 33, 375-384. Glen, Robert. “Developing tools and standards in molecular informatics.” Chemical Communications, 2002, (23), 2745-2747. Hann, Mike; Green, Richard. “Chemoinformatics—a new name for an old problem?” Current Opinion in Chemical Biology, 1979, 3, 379-383. Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. “Experimental and computational approaches to estimate the solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 1997, 23, 3-15. Rosso, Eugene. “Chemistry plans a structural overhaul.” Nature (Naturejobs) 12 September 2002, 419(6903). http://www.nature.com/naturejobs/careersandrecruitment/2002.html Rothman, L. David. “Information management for research in the chemical industry.” Abstracts of Papers, 223rd ACS National Meeting, Orlando, FL, United States, April 7-11, 2002 (2002), CINF-044. Smith, Chris. “Cheminformatics: Redefining the crucible.” The Scientist, 2002, 16(8), 40.