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B.Honarparvar , H.G . Kruger, T. Govender , G.E . M. Maguire

Pentacycloundecane lactam vs lactone norstatine type HIV protease inhibitors : binding energy calculations and DFT study. B.Honarparvar , H.G . Kruger, T. Govender , G.E . M. Maguire

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B.Honarparvar , H.G . Kruger, T. Govender , G.E . M. Maguire

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  1. Pentacycloundecane lactam vs lactone norstatine type HIV proteaseinhibitors: binding energy calculations and DFT study B.Honarparvar,H.G. Kruger,T. Govender,G.E. M. Maguire Catalysisand Peptide Research Unit, School ofHealthSciences, University ofKwaZulu-Natal, South Africa Honarparvar@ukzn.ac.za December 2013

  2. Structuresof PCU-lactam-EAIS, its tautomer PCU-lactim-EAIS, PCU-lactone-EAIS inhibitorsand PCU-models

  3. Objectives • MD simulation • Binding free energy calculations • DFT study

  4. Binding free energy calculations Software: Amber12 Method: MMPB(GB)SA

  5. PCU- peptide inhibitor inside the active site of South African HIV protease

  6. PCU-peptide inhibitor docked to HIV protease

  7. MM-PB(GB)SA binding free energy calculations The MM-PB(GB)SA method can be conceptually summarized as: ΔGbind = Gcomplex – (Genzyme + Gligand) where Gcomplex, Genzymeand Gligand are the free energies of the complex, the enzyme and the ligand, respectively.

  8. Binding free energies and its components for the PCU-models complexed with the HIV protease

  9. Binding free energies and its components for the PCU-peptides complexedwith the HIV protease

  10. Binding free energies and its components for the synthesized PCU-peptides complexed with the HIV protease

  11. DFT study of PCU-models Software: Gaussian09 Method: B3LYP Basis set: 6-311G**

  12. Electronic structure properties Electrostatic Potential Map Polarizability NBO Analysis Natural atomic charges (HOMO- LUMO)

  13. Natural atomic charges (a.u.) on nitrogen and oxygen nuclei of PCU-models

  14. Electrostatic Potential Map PCU-lactone PCU-lactam PCU-lactim

  15. The frontiers orbitalsofPCU-models (a) HOMO for Lactam (b) LUMO for Lactam (a) HOMO for Lactim (b) LUMO for Lactim (a) HOMO for Lactone (b) LUMO for Lactone

  16. Polarizability (Å3), dipole moment (Debye) and Gibbs free solvation energy ∆Gsolv (kcal/mol) values of thePCU-models

  17. Acknowledgements • We thank the National Research Foundation for financial support, UKZN, and the CHPC (www.chpc.ac.za) for computational resources.

  18. Thank you for your kind attention

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