JCICS Major Research Areas

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

2 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

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

4 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

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

6 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. 6

7 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. 7

8 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 8

9 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) 9

10 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), A review with 87 references 10

11 Controlled Vocabulary Indexing of the Manly Article Chemistry High throughput screening Drug screening Bioinformatics Combinatorial chemistry Drug design Molecular modeling Pharmacokinetics Combinatorial library 11

12 Informatics Components (per Dow Chemical Visitors) Architecture LIMS Substance Registry Components of an Informatics System Integration & User Interface Electronic Records Mgmt Process Data Mgmt 12

13 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. 13

14 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. 14

15 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) 15

16 Forthcoming Books Leach, Andrew R.; Gillet,, Valerie J. An Introduction to Chemoinformatics. Kluwer,, expected date of publication: June Gasteiger,, Johann J., ed. Handbook of Chemoinformatics: : From Data to Knowledge. 4 v. Wiley- VCH, expected date of publication August ISBN Engel, Thomas. Chemoinformatics: : A Textbook. Wiley- VCH, expected date of publication: August ISBN

17 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,, Reviews in Computational Chemistry. Wiley-VCH, Paris, Greg. Bibliography: Chemical Information Retrieval and 3D Searching. panizzi.shef.ac..ac.uk/cisrg/links/grep/chemdb.4.html SIRCh: : Chemical Informatics Home Page at Indiana University indiana.edu/~ /~cheminfo/informatics/cinformhome.html 17

18 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. 18

19 Bibliography Brown, F.K. Chemoinformatics Chemoinformatics,, what it is and how does it impact drug discovery. Annual Reports in Medicinal Chemistry, 1998, 33, Glen, Robert. Developing tools and standards in molecular informatics. Chemical Communications, 2002, (23), Hann,, Mike; Green, Richard. Chemoinformatics Chemoinformatics a a new name for an old problem? Current Opinion in Chemical Biology, 1979, 3, 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, ews, 1997, 23, Rosso,, Eugene. Chemistry plans a structural overhaul. Nature (Naturejobs)) 12 September 2002, 419(6903). naturejobs/careersandrecruitment/2002.html Rothman, L. David. Information management for research in the chemical industry. Abstracts of Papers, 223rd ACS National Meeting, Orlando, O FL, United States, April 7-11, (2002), CINF-044. Smith, Chris. Cheminformatics Cheminformatics: : Redefining the crucible. The Scientist, 2002, 16(8),