Chemoinformatics, cheminformatics, chemical informatics: What is it?

1. Chemoinformatics, cheminformatics, chemical informatics: What is it? Gary Wiggins C371 August 2004

2. Jürgen Bajorath on Chemoinformatics, etc. • Chem-, chemi-, or chemo-informatics • Focus on the information resources needed to optimize the properties of a ligand to become a drug (Frank Brown, 1998) • Decision support by computational means • Drug discovery • Chemical Informatics: the application of information technology to chemistry (not with a specific focus on drug discovery)

3. 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.

4. Related Terms per Bajorath • Chemometrics • Application of statistical methods to chemical data and the derivation of relevant statistical models and descriptors • Increasingly difficult to distinguish between chemometrics and chemoinformatics • Discovery informatics—acknowledges that gaining knowledge from chemical data alone is insufficient for success in drug discovery

5. Bajorath’s Conclusions • Boundaries between bioinformatics and chemoinformatics are fluid • Both should be closely combined or merged to significantly impact biotechnology or pharmaceutical research Bajorath, Jürgen, Ed. Chemoinformatics: Concepts, Methods, and Tools for Drug Discovery. (Methods in Molecular Biology; 275) Humana Press: Totawa, NJ, 2004.

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

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

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

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

10. The Periodic Table of the Elements by Mark Winter

11. What is Chemical Informatics? Chemical informatics is the application of information technology to help chemists investigate new problems and organize, analyze, and understand scientific data in the development of novel compounds, materials, and processes.

12. 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 Management: Storage and retrieval of information • Information Use: Data Analysis, correlation, and application to problems in the chemical and biochemical sciences

13. Specialized Chemistry Degree Options at Indiana University • BS in Informatics with a chemistry or biology cognate (essentially a minor) • MS in Chemical Informatics • MS in Bioinformatics • PhD in Science Informatics (expected Fall 2005) http://www.informatics.indiana.edu • MLS or MIS with a specialization in chemical information http://www.slis.indiana.edu

14. IU’s MS in Chemical Informatics • Developed jointly by the School of Informatics and chemistry departments at IUB and IUPUI • First students admitted at IUPUI in fall 2001 and at IUB in fall 2002 • Graduates: 4 • Currently enrolled: 11

15. Unique Program at IUPUI • Laboratory Informatics track at IUPUI • Instrumentation and data interfacing • Laboratory notebooks • Laboratory Information Management Systems (LIMS)

16. 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

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

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

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

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

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

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

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

27. Informatics Components (per Dow Chemical Visitors)

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. 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. Major Journals • Journal of Chemical Information and Computer Sciences (ACS): to split in 2005 into: • Journal of Chemical Information and Modeling • Journal of Chemical Theory and Computation • 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. Chemical Informatics Textbooks • Leach, Andrew R.; Gillet, Valerie J. An Introduction to Chemoinformatics. Kluwer, 2003. ISBN 1-4020-1347-7 • Gasteiger,Johann;Engel, Thomas. Chemoinformatics: A Textbook. Wiley-VCH, 2003. ISBN 3-527-30681-1 • Bajorath, Jürgen, Ed. Chemoinformatics: Concepts, Methods, and Tools for Drug Discovery. (Methods in Molecular Biology; 275) Humana, 2004. ISBN 1-58829-261-4

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, 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 • SIRCh: Chemical Informatics Home Page at Indiana University http://www.indiana.edu/~cheminfo/informatics/cinformhome.html

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. 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, 1999, 3(4), 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.