Molecular Dynamics of the Avian Influenza Virus Team
- Slides: 43
Molecular Dynamics of the Avian Influenza Virus Team Members: Ashvin Srivatsa, Michael Fu, Ellen Chuang, Ravi Sheth Team Leader: Yuan Zhang
Contents • • Influenza Background How Influenza Works Molecular Dynamics Objective Procedure Results Conclusion
Influenza Background
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
Historical Flu Pandemics • 1918 Spanish Flu (H 1 N 1) – 500, 000 deaths in U. S. • 1957 Asian Flu (H 2 N 2) – 69, 800 deaths in U. S. • 1968 Hong Kong Flu (H 3 N 2) – 33, 800 deaths in U. S.
Avian Influenza • H 5 N 1 • 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
How Influenza Works
Structure of Bird Flu Virus • Protein Coat – Hemagglutinin – bonds virus to cell membrane – Neuraminidase – helps virus reproduce in cell • Lipid Membrane • RNA
Lifecycle of Bird Flu Virus • Enters and infects cell • Reproduce genetic material • Cell lyses, releasing new viruses
Fusion Peptide • Part of Hemagglutinin protein • Binds virus to cell membrane
Molecular Dynamics
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
MD Software • Many different types of software solutions exist • We utilized VMD and NAMD – Visual Molecular Dynamics – NAMD 2 – Not (just) Another Molecular Dynamics program
A silicon nanopore, rendered with VMD by the Theoretical and Computational Biophysics Group at the University of Illinois at Urbana-Champaign
Objective
Objective 1. Utilize VMD and NAMD 2 to conduct simulations of the influenza fusion peptide being inserted into a lipid membrane on OSC’s supercomputer clusters 2. Determine how various mutations of the fusion peptide affects its ability to penetrate a lipid membrane
Procedure
Procedure 1. Acquire protein structure files (. pdb) – pdb. org 2. Generate lipid membrane, position protein on membrane 3. Solvate (immerse in water) the protein 4. Create batch files that tell supercomputer what to do
Procedure (Cont. ) 5. Perform an equilibration simulation to equilibrate protein 6. Execute simulation that pulls protein into membrane 7. Produce visualization
Results
Fusion Peptide Equilibration (H 1 N 1)
Fusion Peptide Pulling (H 1 N 1)
Fusion Peptide Pulling #2 (H 1 N 1)
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
Comparison of Amino Sequences • Different Strains of the 20 amino acid fusion peptide • Mutation Names – based on original amino acid, position, and new amino acid
Mutation 1 • Mutation at the “head” of the protein • Variants G 1 V, G 1 S – (Changes to Valine, Serine) • Changes way each peptide enters the membrane (Li, Han, Lai, Bushweller, Cafisso, Tamm)
G 1 V(green), G 1 S (red) mutants, H 1 N 1 (orange)
G 1 V(green), G 1 S (red) mutants, H 1 N 1 (orange)
Analysis • The H 1 N 1 maintains a straight structure • G 1 V, G 1 S variants bunch up – reduce efficiency • Shows that the Glycine is important amino acid on the “head”
Mutation 2 • Mutation near bend in peptide • W 14 A / H 3 N 2 • Boomerang structure is critical to peptide (Lai, Park, White, Tamm)
W 14 A(green), H 1 N 1 (blue)
W 14 A(green), H 1 N 1 (blue)
Analysis • W 14 A bunches up, after going in half way, comes back out • H 1 N 1 maintains structure • Shows that “boomerang” or bend is essential • Also could have contributed the success of the 1918 H 1 N 1 outbreak, compared to H 3 N 2
Mutation 3 • N 12 G • Affects Boomerang Structure • Chosen by team members (not previously attempted)
N 12 G(orange), H 1 N 1 (blue)
N 12 G(orange), H 1 N 1 (blue)
Analysis • N 12 G bunches up halfway through • Does not insert as much as H 1 N 1 • Further proves that proper bend is essential
Conclusion
Conclusions • Boomerang structure of the fusion peptide is essential for proper insertion • Glycine is essential in the “head” position of the fusion peptide
The Bigger Picture • The fusion peptide process is a target for drug intervention • Influenza mutates quickly • Deadly implications if H 5 N 1 mutates to spread from human to human • Further research is essential to protect humans from another pandemic
Acknowledgements Yuan Zhang (project leader) Barbara Woodall (UNIX) Elaine Pritchard (Organization) Brianna, Daniel (Dorm Supervisors) SI Sponsors Parents VMD (University of Illinois) NAMD 2 (University of Illinois) Clustal. W (Amino Acid Alignment) OSC (Supercomputing Time)
Questions?
- Low pathogenic avian influenza
- Virus de la influenza
- Influenza virus replication
- Dispersal definition
- Swine digestive system
- Ahas bash
- Chordata aves
- Avian taxonomy
- Ahas bam
- Dinosauria
- Porter novelli healthstyles survey
- Bird digestive system functions
- Similar sire similar scion
- Ionic covalent metallic
- Zinc oxide + nitric acid → zinc nitrate + water
- Physical state of covalent compounds
- Influenza ww1
- Causative agent
- Stomach flu vs influenza
- The great influenza rhetorical analysis essay
- Is influenza a airborne disease
- Influenza
- Influenza vaccine dosage chart 2019-2020
- Raggio di influenza materozza
- Influenza
- Molecular dynamics limitations
- Plagiarism warning
- Team dynamics france
- Bureaucratic bypass syndrome
- Team spirit becomes team infatuation
- The white team cheers for the blue team, just like
- Vẽ hình chiếu vuông góc của vật thể sau
- Công thức tiính động năng
- Thế nào là mạng điện lắp đặt kiểu nổi
- Tỉ lệ cơ thể trẻ em
- Lời thề hippocrates
- Vẽ hình chiếu đứng bằng cạnh của vật thể
- Quá trình desamine hóa có thể tạo ra
- Các môn thể thao bắt đầu bằng tiếng nhảy
- Hình ảnh bộ gõ cơ thể búng tay
- Sự nuôi và dạy con của hươu
- điện thế nghỉ
- Các loại đột biến cấu trúc nhiễm sắc thể
- Nguyên nhân của sự mỏi cơ sinh 8