1 / 43

Molecular Dynamics of the Avian Influenza Virus

Contents. Influenza BackgroundHow Influenza WorksMolecular DynamicsObjectiveProcedureResultsConclusion. Influenza Background. . The Influenza Problem. ?Flu"Common viral infection of lungsMany different strains which mutate regularlyDifferent levels of virulenceKills roughly half a million people per year.

esmerelda
Download Presentation

Molecular Dynamics of the Avian Influenza Virus

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

    1. Molecular Dynamics of the Avian Influenza Virus Team Members: Ashvin Srivatsa, Michael Fu, Ellen Chuang, Ravi Sheth Team Leader: Yuan Zhang

    2. Contents Influenza Background How Influenza Works Molecular Dynamics Objective Procedure Results Conclusion

    3. Influenza Background

    4. The Influenza Problem “Flu” Common viral infection of lungs Many different strains which mutate regularly Different levels of virulence Kills roughly half a million people per year

    5. Historical Flu Pandemics 1918 Spanish Flu (H1N1) 500,000 deaths in U.S. 1957 Asian Flu (H2N2) 69,800 deaths in U.S. 1968 Hong Kong Flu (H3N2) 33,800 deaths in U.S.

    6. Avian Influenza H5N1 Form of Influenza A Virus One of the most virulent strains today, spreads only from birds to humans Similar to human “common flu” Mutates frequently, makes it hard to develop countermeasures If a mutation allows for it to spread from human to human, pandemic would follow

    7. How Influenza Works

    8. Structure of Bird Flu Virus Protein Coat Hemagglutinin – bonds virus to cell membrane Neuraminidase – helps virus reproduce in cell Lipid Membrane RNA

    9. Lifecycle of Bird Flu Virus

    10. Fusion Peptide Part of Hemagglutinin protein Binds virus to cell membrane

    11. Molecular Dynamics

    12. Molecular Dynamics (MD) Involves study of computer simulations that allow molecules and atoms to interact Extremely complex, based on physics laws Must be run on powerful supercomputers

    13. MD Software Many different types of software solutions exist We utilized VMD and NAMD VMD – Visual Molecular Dynamics NAMD2 – Not (just) Another Molecular Dynamics program

    15. Objective

    16. Objective Utilize VMD and NAMD2 to conduct simulations of the influenza fusion peptide being inserted into a lipid membrane on OSC’s supercomputer clusters Determine how various mutations of the fusion peptide affects its ability to penetrate a lipid membrane

    17. Procedure

    18. Procedure Acquire protein structure files (.pdb) – pdb.org Generate lipid membrane, position protein on membrane Solvate (immerse in water) the protein Create batch files that tell supercomputer what to do

    19. Procedure (Cont.) Perform an equilibration simulation to equilibrate protein Execute simulation that pulls protein into membrane Produce visualization

    21. Results

    25. Next Step: Mutations Random change in genetic material Changes amino acid structure in proteins New strains of influenza arise through random mutations as well as through natural selection

    26. Comparison of Amino Sequences

    27. Mutation 1 Mutation at the “head” of the protein Variants G1V, G1S (Changes to Valine, Serine) Changes way each peptide enters the membrane (Li, Han, Lai, Bushweller, Cafisso, Tamm)

    30. Analysis The H1N1 maintains a straight structure G1V, G1S variants bunch up – reduce efficiency Shows that the Glycine is important amino acid on the “head”

    31. Mutation 2 Mutation near bend in peptide W14A / H3N2 Boomerang structure is critical to peptide (Lai, Park, White, Tamm)

    34. Analysis W14A bunches up, after going in half way, comes back out H1N1 maintains structure Shows that “boomerang” or bend is essential Also could have contributed the success of the 1918 H1N1 outbreak, compared to H3N2

    35. Mutation 3 N12G Affects Boomerang Structure Chosen by team members (not previously attempted)

    38. Analysis N12G bunches up halfway through Does not insert as much as H1N1 Further proves that proper bend is essential

    39. Conclusion

    40. Conclusions Boomerang structure of the fusion peptide is essential for proper insertion Glycine is essential in the “head” position of the fusion peptide

    41. The Bigger Picture The fusion peptide process is a target for drug intervention Influenza mutates quickly Deadly implications if H5N1 mutates to spread from human to human Further research is essential to protect humans from another pandemic

    42. Acknowledgements Yuan Zhang (project leader) Barbara Woodall (UNIX) Elaine Pritchard (Organization) Brianna, Daniel (Dorm Supervisors) SI Sponsors Parents

    43. Questions?

More Related