Jean-Claude Bradley presents at the Opal Events 3rd Annual Drug Discovery Partnership: Filling the Pipeline on Pre-competitive Collaboration: Sharing Data to Increase Predictability

1. Pre-competitive Collaboration: Sharing Data to Increase Predictability 3rd Annual Drug Discovery Partnership: Filling the Pipeline Jean-Claude Bradley Associate Professor of Chemistry Drexel University October 17, 2011

2. Opportunities for Competitive Collaboration

3. Industry is Sharing More

4. Solubility and Melting Points are critical properties in the drug discovery process

5. Data quality is essential for both measurements and predictions based on measurements

6. Openness is proving to be a powerful tool for assessing the reliability of data

7. Solubility prediction for Taxol using Abraham descriptors Pred Exp

8. Predicted temperature dependent solubility of Taxol in water based on melting point (M)

10. Merck Index

11. Chemical Vendor Catalogs (e.g. Sigma-Aldrich)

12. Peer-Reviewed JournalsSingle values don’t tend to be contradicted

13. Question Assumptions Using technology, we can begin to replace the “trusted source” model with one based on transparency and provenance

14. The Chemical Information Validation Sheet 567 curated and referenced measurements from Fall 2010 Chemical Information Retrieval course

15. Discovering outliers for melting points (stdev/average)

16. Investigating the m.p. inconsistencies of EGCG

17. Investigating the m.p. inconsistencies of cyclohexanone

18. Most popular data sources

19. Alfa Aesar donates melting points to the public

20. Open Melting Point Explorer (Andrew Lang)

21. Outliers MDPI dataset PhysProp (EPA donated all data to public also)

22. Outliers for ethanol: Alfa Aesar and Oxford MSDS

23. Inconsistencies and SMILES problems within MDPI dataset

24. MDPI Dataset labeled with High Trust Level

25. Open Melting Point Datasets Currently 27,000 mps for 20,000 compounds

26. What is the melting point of 4-benzyltoluene? American Petroleum Institute5 C PHYSPROP-30 C PHYSPROP 125 C peer reviewed journal (2008)97.5 C government database-30 C government database4.58 C

27. The quest to resolve the melting point of 4-benzyltoluene: liquid at room temp and can be frozen <-30C (Evan Curtin)

28. Open Lab Notebook page measuring the melting point of 4-benzyltoluene

29. Motivation: Faster Science,Better Science

30. Ruling out all melting points above -15C?

31. Oops – 4-benzyltoluene freezes after 16 days at -15C!

32. Measuring the melting point by slowly heating from -15 C gives 5 C

33. There are NO FACTS, only measurements embedded within assumptions Open Notebook Science maintains the integrity of data provenance by making assumptions explicit

34. TRUST PROOF

35. Common errors in datasets multiple melting points for the same compound in the same database stereochemistry issues sign inversion conversion errors (Kelvin/Celcius Fahrenheit/Celcius) bad SMILES (non-rendering) salts associated with SMILES for free base using boiling point for melting point

36. Open Random Forest modeling of Open Melting Point data using CDK descriptors (Andrew Lang) R2 = 0.78, TPSA and nHdon most important

37. Melting point prediction service

38. Melting point predictions and measurements on iPhone/iPad (Andrew Lang and Alex Clark)

39. Publication of double+ validated melting point dataset to Nature Precedings and LuLu

42. Crowdsourcing Solubility Data

43. ONS Challenge Judges

44. ONS Challenge Award Winners

45. Web services for summary data (Andrew Lang)

46. Reaction Attempts Book

47. Reaction Attempts Book: Reactants listed Alphabetically

49. Interactive NMR spectra using JSpecView or ChemDoodleand the Open JCAMP-DX format

50. Predicting Best Solvent for Imine Formation using solubility and melting point data (Evan Curtin)

51. Predicting Yield of Imine Formation in Ethanol (Evan Curtin)

52. Google Apps Scripts web services

53. Google Apps Scripts for conveniently exploring melting point data

54. Comparison of model with triple validated measurements Straight chain carboxylic acids from 1 to 10 carbons Straight chain alcohols from 1 to 10 carbons

55. Cyclic primary amines from 3 to 6 carbons (cyclobutylamine flagged for validation – only single source available)

56. Google Apps Scripts for planning reactions and creating schemes

57. Open Melting Points in Supplementary Data Pages of Wikipedia (Martin Walker)

58. All ONS web services

59. Some Initiatives Promoting More Openness in Drug Discovery

60. Open Primary Research in Drug Design using Web2.0 tools (malaria)(blogs, wikis, Second Life, mailing lists) Rajarshi Guha Indiana U Tsu-Soo Tan Nanyang Inst. Docking JC Bradley Drexel U Synthesis Phil Rosenthal UCSF (malaria) Dan Zaharevitz NCI (tumors) Testing

61. Outcome of Guha-Bradley-Rosenthal collaboration

63. Open Notebook Science can be a useful tool in this context