1. 1 PowerMV Chemical Data Mining Environment S. Stanley Young Jun Feng and Jack Liu NISS MPDM, McMaster University 4 June 2005

2. 2 Outline 1.PowerMV, a chemistry data mining environment. 2.rSVD, robust singular value decomposition, Liu, Hawkins, Ghosh,Young, PNAS (2003). 3.Space-filling designs. 4.PharmID: complex problem.

3. 3 Environment 20k lines of interface code; 300k lines of algorithm code. ~0.75 man-years.

4. 4 SD File, 50 years old and bad! 1 -ISIS- 3D 20 22 0 0 0 0 0 0 0 0999 V2000 2.0680 1.5173 0.0000 C 0 0 0 0 0 2.9340 2.0173 0.0000 N 0 0 0 0 0 2.9340 3.0173 0.0000 C 0 0 0 0 0 3.8000 1.5173 0.0000 C 0 0 0 0 0 3.8000 0.5173 0.0000 C 0 0 0 0 0 4.6660 0.0173 0.0000 C 0 0 0 0 0 4.6660 -0.9827 0.0000 N 0 0 0 0 0 5.5321 -1.4827 0.0000 C 0 0 0 0 0 5.5321 -2.4827 0.0000 C 0 0 0 0 0 4.6660 -2.9827 0.0000 S 0 0 0 0 0 3.8000 -2.4827 0.0000 C 0 0 0 0 0 3.8000 -1.4827 0.0000 C 0 0 0 0 0 2.9061 -0.9480 0.0000 C 0 0 0 0 0 2.0000 -1.4619 0.0000 C 0 0 0 0 0 2.0000 -2.5035 0.0000 C 0 0 0 0 0 2.9061 -3.0173 0.0000 C 0 0 0 0 0 6.4260 -3.0173 0.0000 C 0 0 0 0 0 7.3321 -2.5035 0.0000 C 0 0 0 0 0 7.3321 -1.4619 0.0000 C 0 0 0 0 0 6.4260 -0.9480 0.0000 C 0 0 0 0 0 1 2 1 0 0 0 2 3 1 0 0 0 2 4 1 0 0 0 4 5 1 0 0 0 5 6 1 0 0 0 Etc.

5. 5 Smiles Chemical Notation CC1=CC=C(C=C1)S(=O)(=O)N(CC(O)=O)C2=CC(Cl)=CC=C2 CC1CCC(CC1)C(C)(C)C(CC(C)C)C2CCCC(C)C2

6. 6 Viewer

7. 7 Molecule Blow Up

8. 8 3D View

9. 9 Compute Molecular Descriptors, Drug-Like Properties

10. 10 Chemical Graphs and Properties

11. 11 Multiple Descriptor Types Numerical Topology!

12. 12 Similarity Searching, Motivating Paper

13. 13 Select a Target Compound

14. 14 Search Dialog

15. 15 Structure Comparison Window Target Neighbor Annotation

16. 16 Statistical Methods

17. 17 Free download : www.niss.org/PowerMV Summary Display SD. Compute descriptors. Cluster. Statistical analysis. Similarity search. Become NISS affiliate! 20k display code 300k algorithm code

18. 18 Contact Information Stan Young young@niss.org www.niss,org 919 685 9328 Jun Feng feng@niss.org Become a NISS Affiliate!

19. 19 Questions / Comments ?

20. 20 Computed Properties – Rule of 5

21. 21 Structure Comparison

22. 22 Neighbor List

23. 23 Attribute Comparison

24. 24 Annotated Data Bases 1.Stockwell ACL 2.ChemBank 3.Exploratory Centers for Chemoinformatics Research 4.Chemical Entities of Biological Interest 5.Commercial, e.g. GVK, ACS, MDDR, Ashgate

25. 25 Rule of Five

26. 26 Example: CNS Compounds

27. 27 Current NISS Research PharmID: Pharmacophore Identification Finds multiple binding modes! Selectivity. 1.NISS research. 2.Jun Feng, CompChem. 3.Seeking collaborators. 4.Become NISS affiliate.