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) 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, Brown, F.K. “Chemoinformatics, what it is and how does it impact drug discovery.” Annual Reports in Medicinal Chemistry, 1998, 33,

4 Related Terms per Bajorath Chemometrics Application of statistical methods to chemical data and the derivation of relevant statistical models and descriptors Application of statistical methods to chemical data and the derivation of relevant statistical models and descriptors Increasingly difficult to distinguish between chemometrics and chemoinformatics 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 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, 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, 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!

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 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

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) MLS or MIS with a specialization in chemical information

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 Instrumentation and data interfacing Laboratory notebooks Laboratory notebooks Laboratory Information Management Systems (LIMS) Laboratory Information Management Systems (LIMS)

16 Graduate Courses in Chemical Informatics at Indiana University C571 Chemical Information Technology C572 Molecular Modeling & Computational Chemistry

17 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

18 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

19 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

20 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

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

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 Potency Absorption Absorption Distribution Distribution Metabolism Metabolism Elimination 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), 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) Architecture LIMSComponents of an InformaticsSystem Electronic Records Mgmt SubstanceRegistry Process Data Mgmt Integration & User Interface

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 Information and Modeling Journal of Chemical Theory and Computation 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, ISBN Gasteiger,Johann;Engel, Thomas. Chemoinformatics: A Textbook. Wiley-VCH, ISBN Bajorath, Jürgen, Ed. Chemoinformatics: Concepts, Methods, and Tools for Drug Discovery. (Methods in Molecular Biology; 275) Humana, ISBN

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, Gasteiger, Johann J., ed. Handbook of Chemoinformatics: From Data to Knowledge. 4 v. Wiley-VCH, ISBN Reviews in Computational Chemistry. Wiley-VCH, Paris, Greg. Bibliography: Chemical Information Retrieval and 3D Searching. SIRCh: Chemical Informatics Home Page at Indiana University

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, Glen, Robert. “Developing tools and standards in molecular informatics.” Chemical Communications, 2002, (23), Hann, Mike; Green, Richard. “Chemoinformatics—a new name for an old problem?” Current Opinion in Chemical Biology, 1999, 3(4), 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, Rosso, Eugene. “Chemistry plans a structural overhaul.” Nature (Naturejobs) 12 September 2002, 419(6903). 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.