Molecular Dynamics of the Bird Flu Virus

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Molecular Dynamics of the Bird Flu Virus

• Presented By Team Tamiflu
• Maya Madhavan, Sapan Bhuta, Kevin Hawkins, and
  Saptarshi Chaudhuri
• Led By Yuan Zhang

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What is Bird Flu?

• The Flu
• Is a common viral infection of lungs
• Affects millions of people annually
• A leading cause of death in the United States
• Bird flu (H5N1)
• Caused by avian (bird) influenza (flu) viruses
• Occurs naturally among birds
• Humans have limited immunity to this subtype
• killed 100 million birds since 2003
• Infected 313 human, killed 191since 2003 (Data as
  of June 15, 2007)

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Under Electron Microscope
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Influenza Throughout History

• 1918 Spanish Flu (H1N1)
• killed 20 million
• people worldwide,
• 500,000 in US
• 1957 Asian Flu (H2N2)
• Killed 69,800 people in US
• 1968 Hong Kong Flu (H3N2)
• Killed 33,800 people in US

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How Bird Flu Works
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Structure of the Bird Flu Virus

• Protein Coat
• Hemagglutinin (HA)
• Neuraminidase (NA)
• Lipid Membrane
• Lipid Bilayer envelope
• RNA Genetic Material
• 8 segments
• Negative sense
• Encode viral protein

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The Life Cycle of Flu Virus
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The Peptide in Question
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The 20 amino acid Fusion Peptide (1 IBN)
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Project Objective

• The original objective
• Simulate the Hemagglutinin fusion peptides
  interaction with the host cell membrane.
• The extended objective
• Understand how the evolution of the Hemagglutinin
  fusion peptide has affected its efficiency in the
  invasion process.

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Tools

• Molecular dynamics packages
• NAMD (Not Another Molecular Dynamics)
• Uses OSC supercomputer to simulate protein
  movements and interactions
• Returns input files for VMD
• VMD (Visualization of Molecular Dynamics)
• Scales, rotates, and translates structures
• Changes color and representation
• Plays simulations using NAMD data
• Creates movies
• UNIX
• Creates batch scripts to send to supercomputer
  for NAMD processing
• Manipulates simulation parameter files

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Methodology

• Acquire the protein structure from the protein
  data bank (pdb.org)
• Configure simulation parameter files using UNIX
• Use batch processing scripts to send simulation
  program to the supercomputer for parallel
  processing
• NAMD runs the simulation and sends back output
  files
• Load the output data into VMD and visualize the
  protein
• Look at the structural change of the protein
  using molecular dynamics packages
• Play the simulation and change representations
• Create an animation of the protein structure

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Simulations

• Of The 20 amino acid Fusion Peptide (1IBN)

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• Fusion Peptide Maintaining Equilibrium in a Water
  Sphere

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Fusion Peptide Isolated For Viewing While
Maintaining Equilibrium
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Fusion Peptide in a Water Sphere with One Atom
Pulling with Constant Velocity
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Isolated Fusion Peptide Pulling with Constant
Velocity
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Fusion Peptide in a Water Sphere with All Atoms
Moving
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Isolated Fusion Peptide with All Atoms Moving
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Fusion Peptide Maintaining Equilibrium While
Attached to a Cell Membrane
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Fusion Peptide Inserting Itself into the Cell
Membrane
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The Bird Flu Scare?
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Intro 1933 Fusion Peptide

• 1933 H1N1 Illinois outbreak
• Genetic Difference from Bird Flu fusion peptide
• W14A (95 similar)
• Structural Difference makes fusion peptide less
  efficient in transmission

Yellow Peptide 1933 Illinois Outbreak Blue
Peptide 1997 Bird Flu
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Bird Flu More Like Spanish Flu?

• 1933 peptide 85 alike to 1918
• Bird Flu 90 alike to 1918

BLAST
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1933 Illinois Outbreak Vs. 1997 Bird Flu Outbreak
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Simulation Explanation

• After ½ of simulation, no more insertion occurs
  for the 1933 peptide, reducing the efficiency of
  the peptide invasion
• While the 1997 on the right membrane is flattened
  and folds over
• Bird Flu enters the cell with greater efficiency
  than the 1933 peptide due to structural
  differences

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What does it all mean? And How Does It Affect Us?

• Influenza mutates very quickly
• If H5N1 mutates to be transmissible between
  humans another pandemic could occur similar to
  the Spanish Flu
• Death toll possibly exceeding 50 million

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Prospects Our Future and The Future of the Bird
Flu Virus

• Further research on the influenza virus through
  new technology will provide us with new
  strategies for earlier diagnosis, prevention, and
  a better design for antiviral drugs and
  vaccinations.

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Acknowledgements

• Yuan Zhang
• (For All The Project Help!)
• Elaine Landwehr
• (For Having Us!)
• Barbara Woodall
• (For All the Unix Help!)
• And the OSC staff

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• OH!!! Wait Parents too!

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• For PAYING for our trip )