thua ie d - amazon s3...1 gem4 summer school 2006 cell and molecular mechanics in biomedicine august...
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GEM4 Summer School 2006Cell and Molecular Mechanics in BioMedicineAugust 7–18, 2006, MIT, Cambridge, MA, USA
“Reactions”,Energy Landscapes
& KineticsPat Doyle
[email protected] Engineering Dept.
MIT
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Key References
• Mechanics of Motor Proteins & the Cytoskeleton,J. Howard
• Biophysical Chemistry, C. Cantor and P. Schimmel
• Mechanical Processes in Biochemistry, Bustamante etal., Ann. Rev. Biochem., 73, 705-748, 2004
• Brownian Motion in a Field of Force and the DiffusionModel of Chemical Reactions, H.A. Kramers, Physica, 4,284-304, 1940
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“Reactions”
Fisher, Marszalek & Fernandez, Nature 2000
Binding of TAT box-binding protein
Titin unfolding
RNA unfolding
Receptor-ligand
DNA-protein
Bustamante et al. 1997
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Diffusion Limited Reactions
5Geometry matters…
Some details….
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First Passage Time
Need to input U(x) to solve…..
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Relaxation time of a damped spring
Exponential Effect of Barrier Height
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Details of Derivation…
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Things that Affect Energy Landscapes
• Force (pulling/pushing, rate)• Enzymes (catalysts)• Salt, pH• “additives” (protein drug stabilization)• ….
17Strick, Allemand, Bensimon, Croquette, Ann. Rev. Biophys. 2000
Two State Example: Protein Unfolding
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Force Changes the Energy Landscape
Bustamante et al., Ann. Rev. Biochem. 2004