Dissertation > Excellent graduate degree dissertation topics show

Free Energy Calculations and Binding Analysis of Two Potential Anti-influenza Drugs with Polymerase Basic Protein-2 (PB2)

Author: LvHuiMin
Tutor: WeiDongQing
School: Shanghai Jiaotong University
Course: Biomedical Engineering
Keywords: Antiviral drugs for influenza Alkaline polymerase 2 (PB2) Docking Molecular dynamics simulations Molecular mechanics / generalized Byrne solvent accessibility area free energy calculation method
CLC: R511.7
Type: Master's thesis
Year: 2011
Downloads: 50
Quote: 0
Read: Download Dissertation

Abstract


Influenza (flu) is an acute respiratory infection caused by the influenza virus each year in the crowd has a significant morbidity and mortality. Now develop antiviral drugs for influenza can be broadly divided into two categories, a class of drug targets for the virus surface glycoprotein neuraminidase, a class of proton channel M2 protein drug targets. However, the high mutation rate of the influenza virus genome, with the extensive use of the existing anti-influenza virus drugs, even abuse these drugs increasingly large proportion of resistant strains of the virus. Development of new anti-influenza virus is an effective means to address the treatment of influenza, and respond to large-scale outbreak of the flu. Alkaline polymerase of the influenza virus polymerase 2 (PB2) subunit plays an important role for the replication of influenza virus, PB2 and host cells of the mRNA 5 'end cap structure of the binding is the initial step of the virus protein synthesis. Therefore PB2 drug targets selected in our experiments. The docking 10ns molecular dynamics simulations (MD) were analyzed binding domain of the PB2 cap-like structure and small molecule RO, PPT28, as well as the combination of the cap structure analogues m7GTP. Molecular mechanics / generalized Byrne solvent accessible surface area (MM / GBSA) calculated from a combination of its own use can show, RO and PPT28 can be combined and PB2 better than m7GTP. Forming the hydrophobic interaction between the RO, PPT28 hydrophobic portion of the binding groove of hydrophobic residues for stabilizing the binding of small molecules and PB2 has an important contribution. And the small molecule has a total of six - five - membered ring in the binding grooves has a relatively fixed position, also plays an important role in the binding of small molecules and PB2. MRNAs in eukaryotic cells, the 5 'end cap structure also plays a vital role for eukaryotic own mRNA translation. Eukaryotic translation initiation factor 4E (eukaryotic initiation factor 4E, eIF4E) recognizes and binds to the 5 'end of the mRNAs cap structure, open the assembly of ribosomal subunits, and then, eukaryotes own mRNA translation process to be carried out smoothly . PB2 and eIF4E cap-like structure combined with similarities. In order to ensure that RO PPT28 not hinder the organism's own translation of mRNAs, we were a of eIF4E-m7GTP of eIF4E-RO which eIF4E-PPT28 molecular docking. The docking results, RO and PPT28 not a good combination with eIF4E. In summary, we speculate that RO and PPT28 possible by the combination of the PB2 cap-like structure on the competitive binding groove so as to achieve the role of inhibition of influenza virus replication, while not affecting the host protein synthesis, can be used as anti-influenza virus drug . RO and PPT28 the Inquirer molecular database screening and docking screening elected three of the same potential as the small molecule anti-influenza virus new drugs.

Related Dissertations

  1. Research on Orbital Control Method for Space Rendezvous and Docking,V526
  2. Design and Implementation of Space Rendezvous and Docking Linear Movement Simulator Control System,TP273
  3. Based on particle swarm algorithm for molecular docking,R91
  4. Drug interactions between small molecules and proteins Spectroscopic and Molecular Docking Study,R96
  5. Molecular Modelling of Transmembrane Water Channels Based on Cyclic Peptide Nanotubes,TB383.1
  6. Intvestgation of Ligand Channels and Cooperativity Mechanism in Cytochrome P450s,Q559.9
  7. For small spacecraft cone - rod flexible wall docking mechanism design studies,V526
  8. Jiangxi Vocational Education and employment needs of industrial enterprises in the park of the docking mechanism and improve research,F249.27
  9. HDAC Inhibitiors: Design, Synthesis and Biological Evaluation of Analoges of LBH589,R914
  10. On Investigations between Small Molecule Drugs and Serum Albumins by Optical Spectroscopy and Molecular Computational Modeling,R96
  11. Application of QSAR and Molcular Docking Studies in Medicinal Analytical Chemistry,R917
  12. HIV-1 reverse transcriptase inhibitors QSAR and Molecular Design,R512.91
  13. Gearing Qin Art to Needs of Current Audience,J632.31
  14. The Research on Combine City with Countryside about Liaoning Province’s Person System Reforms,F842.6
  15. Predictions of Human Kinome-Small Molecule Interactions,Q55
  16. Molecular Simulation of Glycerol Dehydrogenase of Gluconobacter Oxydans,TQ920.1
  17. Theoretical Studies on Dimethylarginine Dimethylaminohydrolase-1,TQ226.31
  18. Reflections on the Reforming of the Existing Buildings,TU984.114
  19. Based detail description and building performance analysis BIM design process from research,TU201.4
  20. The Study of Docking Strategy of Multi-Dof Force Loading Platform,U661.72

CLC: > Medicine, health > Internal Medicine > Infectious disease > Viral infections > Influenza
© 2012 www.DissertationTopic.Net  Mobile