1. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk QSAR methods in biomedicine – effect of geometry optimization Åsmund Rinnan

2. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Project Introduction Question Study Results Summary

3. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk What the F**K is QSAR?! Quantitative Structure Activity Relationship Introduction Question Study Results Summary

4. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Closely related compounds O O HO OH O O HO OH CH 3 O O H CO OH 3 F O O HO OH O O HO OH CH 3 3 Introduction Question Study Results Summary

5. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk 2D  3D O O HO OH Introduction Question Study Results Summary

6. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk 3D  Descriptors MW: 270.241 Dipole: 3.44 SASA: 470.87 FISA: 182.33 PISA: 288.54 Volume: 795.13 DonorHB: 2 AccptHB: 3.75 Dip^2/V: 0.0149 Ac*DN^.5/SA: 0.0113 Introduction Question Study Results Summary

7. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk 3D  Descriptors MW: 270.241 Dipole: 3.44 SASA: 470.87 FISA: 182.33 PISA: 288.54 Volume: 795.13 DonorHB: 2 AccptHB: 3.75 Dip^2/V: 0.0149 Ac*DN^.5/SA: 0.0113 Introduction Question Study Results Summary

8. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Descriptors  PLS B And the rest is chemometrics… Introduction Question Study Results Summary Attribute of interest

9. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Diabetes 2 Estrogen  -receptor + Genistein Introduction Question Study Results Summary

10. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Geometry optimization O O HO OH Introduction Question Study Results Summary days sec min h

11. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Accuracy vs. Time UFF AM1 PM3HF B3LYP MechanicalSemi-empirical Density Functional Theorem Time consumption SecondsDays Theoretical level Introduction Question Study Results Summary

12. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Geo Methods Mechanical: Simple, Solving Newton’s equations –UFF: General method –Amber: Good for proteins (doesn’t work yet) Semi-empirical: Simplified quantum chemical Hamiltonian. Parametrized to some experimental values (dependent on method) –AM1 –PM3 Hatree-Fock: Correlation energy is not included DFT – B3LYP: Includes correlation energy - Most advanced method for computing optimization used in this study Introduction Question Study Results Summary

13. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Isoflavonoid derivatives Points of substition Substituens Introduction Question Study Results Summary

14. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Data UFF AM1 PM3 HF B3LYP Introduction Question Study Results Summary

15. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Methods Leave-one out cross-validation Introduction Question Study Results Summary

16. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Methods Variable selection Introduction Question Study Results Summary

17. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Raw data Introduction Question Study Results Summary

18. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Variable selection Introduction Question Study Results Summary

19. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Future work 2/3 more datasets Descriptors from different softwares Variable selection Cross-Model-Validation Introduction Question Study Results Summary

20. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk THE END Thanks are due to: –Søren Balling Engelsen –Niels Johan Christensen Thank you for your attention… Introduction Question Study Results Summary