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BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark QxPR methods in biomedicine.

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Presentation on theme: "BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark QxPR methods in biomedicine."— Presentation transcript:

1 BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark 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 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 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 Basic of QSxR 3D  Descriptors MW: Dipole: 3.44 SASA: FISA: PISA: Volume: DonorHB: 2 AccptHB: 3.75 Dip^2/V: Ac*DN^.5/SA:

5 BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark Basic of QSxR 3D  Descriptors MW: Dipole: 3.44 SASA: FISA: PISA: Volume: DonorHB: 2 AccptHB: 3.75 Dip^2/V: Ac*DN^.5/SA:

6 BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark 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 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 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 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 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 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 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 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 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 Data Descriptors

16 BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark 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 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 Results Descriptor package

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


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