1. Custom Spotfire Applications for use in Drug Discovery Chris Louer Team Leader, Cheminformatics © 2001, GlaxoSmithKline, Inc. - All Rights Reserved.

2. Data Source Spectrum OracleFlat FilesExcel

3. Chemical Data Sets  Property calculations on virtual libraries –Web based tools –Excel tables –Flat files –1,000’s to 10,000’s  Screening results –Screening Data Management (SDM) –Discovery Explorer –Biologist  Email  Phone calls –1000’s

4. Property Calculator – Submission Hung, S., Seibel, G, Cheminformatics

5. Property Calculator - Results Hung, S., Seibel, G, Cheminformatics

6. Analysis Needs Chemical Structure

7. Requirements  Attach smiles strings to data  Create easy to install solution  Quick solution  Easy to maintain and upgrade  Keep existing calculators

8. Spotfire – SSV3 Issues  Smiles strings  Virtual compounds not in corporate DB  ISIS DB not simple to build  Multiple data sources

9. Virtual Library Properties

11. Screening Results

13. Substructure Searches

15. Similarity Searches

16. Simple Structure Viewer  No analysis required  Simple structure viewing –Smiles to structure –Based on “Show Marker Data” Plugin  Show on highlight  Minimal real estate

17. Simple Viewer

18. Moving to the Server Side  No client installation –Reduced integration issues –Updates easy to deliver  Simplified navigation  Easy to design  Link existing web application  Supported by Spotfire

19. Structure Viewing  Mol files displayed in chime plugin 1 –Chime functionality included  Smiles converted to mol files on the server –Corina 2  Rule based minimization  Continued development of 3D Calculations 1.MDL Information Systems, Inc., www.mdli.comwww.mdli.com 2.Gasteiger Research, http://www2.ccc.uni-erlangen.de/services/3d.html

20. Web Based Structures

21. Structure Analysis

22. Collaborative Workspace  Many data sets still flat files –Results from multiple sources  Online DB  Email  Excel  Telephone  Increased need for scientific collaboration  Keep results up to date

23. Collaborative Workspace  Web Based  Searchable  Upload data files  Online Discussion  Auto loaded into Spotfire  Validated Templates

24. Collaborative Workspace

26. Discussion Forums

27. Additional Data Sources  Analytical Results –LCMS –CLND –Weight –UV –Spectra

28. Data Merging and Updating Molecular Properties Computational Group Cheminformatics Screening Results Corporate DB Biologist Analytical Results Processing Group LCMS Group ?

29. Data Merging and Updating Pipeline Pilot, SciTegic, www.scitegic.com

30. Future Directions  Re-build infrastructure –Corina structures –3 D property calculations –Better integration  Get user feedback  Tie in to DB results  Move all tools to web

31. Acknowledgements Cheminformatics  Fran Stewart  Sunny Hung  George Seibel  Terry Francis Spotfire  Trish Ward  Jeff Molloy  Cristian Ilie Discovery Research Chemistry  Ralph Rivero  Michael Moore  Todd Graybill  Maria Cichy-Knight  Allison Dunn