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Background. NASA experimented with High Magnetic Fields to simulate zero gravity for experiments on plantsPaul and coworkers found that the magnetic field itself, not just the lack of gravity, was causing stress on the plants. 18.9 T. Control. Paul 2005. . Hypothesis. Strong magnetic fields generate subtle perturbations of biomolecules due to the structural diamagnetic anisotropy of the molecules, causing a disruption of normal biochemical function.
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2. Background NASA experimented with High Magnetic Fields to simulate zero gravity for experiments on plants
Paul and coworkers found that the magnetic field itself, not just the lack of gravity, was causing stress on the plants
3. Hypothesis Strong magnetic fields generate subtle perturbations of biomolecules due to the structural diamagnetic anisotropy of the molecules, causing a disruption of normal biochemical function
4. Transcription
5. T7 RNA Polymerase:The Hand Model
6. Top View
7. 1D Model – No Field
8. 1D Model – Field
9. Energy Analysis
10. Force Analysis
11. Solve for Magnetic Force
12. Is This Force Reasonable? Other molecular forces creating extreme structural alterations: ~10-10-10-11 N
Overstretching DNA
Unfolding Titin (muscle)
Unfolding DNA hairpin
Preventing T7 RNAP from proceeding along the DNA during transcription
13. Conclusions Experimentally,
Some delay in transcript production is indicated at 9 Tesla for T7 RNA polymerase
A reduction in transcript production was observed for SP6 RNA polymerase at 9 Tesla
Theoretically, a more accurate model is needed
Improve k approximations
Improve force estimates
Include other possible deformations
Next: Further test the hypothesis
Analyze experiments at 20 and 25 Tesla
15. Force vs. Field Strength
16. The Thumb
17. References Cheetham, Graham M. T., David Jeruzalmi, and Thomas A Steitz (1999) Structural basis for initiation of transcription from an RNA polymerase-promoter complex. Nature (399) 80-83.
Gopal, Vijaya et al (1999) Characterization of Structural Features Important for T7 RNAP Elongation Complex Stability Reveals Competing Complex Conformations and a Role for the Non-template strand in RNA Displacement. J. Mol. Biol. (290) 411-431
Lu, Hui and Klaus Schulten (1999) Steered Molecular Dynamics Simulations of Force-Induced Protein Domain Unfolding. PROTEINS: Structure, Function, and Genetics (35) 453-463
Paul, A.-L., R.J. Ferl, B. Klingenberg, J.S. Brooks, A.N. Morgan, J. Yowtak, and M.W. Meisel (2005) Strong Magnetic Field Induced Changes of Gene Expression in Arabidopsis. Materials Processing in Magnetic Fields: Proceedings of the International Workshop on Materials Analysis and Processes in Magnetic Fields (NHMFL, Tallahassee, 17-19 March 2004). To appear fall 2005.
Pauling, Linus (1979) Diamagnetic anisotropy of the peptide group. Biophysics (76) 2293-2294.
Sousa, Rui, John Rose and B. C. Wang (1994) The Thumb’s Knuckle: Flexibility in the Thumb Subdomain of T7 RNA Polymerase is Revealed by the Structure of a Chimeric T7/T3 RNA Polymerase. Jol. Mol. Biol. (244) 6-12.
T7 RiboMax Express Large Scale RNA Production System Technical Bulletin. Promega. (www.promega.com)
Tahirov, Tahir H et al. (2002) Structure of a T7 RNA polymerase elongation complex at 2.9 A resolution. Nature (420) 43-50.
Wadelton, Kim et al. (2005) Diamagnetic Anisotropy of T7 RNA Polymerase Report of research preformed Summer 2005 as part of NHMFL REU Program.
Worchester, D.L. (1978) Structural Origins of diamagnetic anisotropy. Pro.Natl. Acad. Sci. (75) 5475-5477.
Worczak, Marianna et al. (2005) Effects of high magnetic fields on in vitro transcription Report of research preformed Summer 2005 as part of NHMFL REU Program.