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BEST - B YG E N S UND T ILVÆRELSE QSAR & C HEMOMETRICS Åsmund Rinnan Royal Veterinary and Agricultural University Denmark QSAR 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 QSAR 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 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 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 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 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 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 3D  Descriptors MW: Dipole: 3.44 SASA: FISA: PISA: Volume: DonorHB: 2 AccptHB: 3.75 Dip^2/V: Ac*DN^.5/SA: 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 3D  Descriptors MW: Dipole: 3.44 SASA: FISA: PISA: Volume: DonorHB: 2 AccptHB: 3.75 Dip^2/V: Ac*DN^.5/SA: 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 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 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 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 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 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 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 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 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 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 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 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 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 THE END Thanks are due to: –Søren Balling Engelsen –Niels Johan Christensen Thank you for your attention… Introduction Question Study Results Summary


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