1. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk QxPR 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 QSxR?! QSAR?? QSPR!? Quantitative Structure Activity or Property Relationship Estrogen  -receptor

3. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Basics of QSxR 2D  3D O O HO OH

4. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Basic of QSxR 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

5. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Basic of QSxR 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

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

7. 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 Basics O O HO OH days sec min h

8. 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 MM3*

9. 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 MM3* 180 Dielectric constant

10. 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 MechanicalSemi-empirical Density Functional Theorem Time consumption SecondsDays Theoretical level Introduction Question Study Results Summary MM3* 6-31g(d,p) Basis sets STO-3g 6-31g B3LYP

11. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Data Datasets O O HO OH Isoflavonoids OH Aglycons Estrogen like compounds

12. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk O O HO OH Isoflavonoids Estrogen like compounds Data Properties Melting point

13. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Data Properties OH Aglycons log P

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 Overview UFF AM1 PM3 HF B3LYP MM3* Melting point log P x 2 x 3

15. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Data Descriptors

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 Validation Leave-one out cross-validation

17. 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 Variable selection: Jack-knifing Principal variables

18. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Results Descriptor package

19. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Results Distance to optimal Aglycons Estrogen-likeIsoflavonoids

20. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Results Prediction quality Aglycons Estrogen-likeIsoflavonoids

21. BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark aar@kvl.dk Conclusion UFF AM1 PM3HF B3LYP MechanicalSemi-empirical Density Functional Theorem Time consumption SecondsDays Theoretical level MM3*