1

GEM4 Summer School 2006Cell and Molecular Mechanics in BioMedicineAugust 7–18, 2006, MIT, Cambridge, MA, USA

“Reactions”,Energy Landscapes

& KineticsPat Doyle

pdoyle@mit.eduChemical Engineering Dept.

MIT

2

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

3

“Reactions”

Fisher, Marszalek & Fernandez, Nature 2000

Binding of TAT box-binding protein

Titin unfolding

RNA unfolding

Receptor-ligand

DNA-protein

Bustamante et al. 1997

4

Diffusion Limited Reactions

5Geometry matters…

Some details….

6

7

8

9

10

11

12

13

First Passage Time

Need to input U(x) to solve…..

14

Relaxation time of a damped spring

Exponential Effect of Barrier Height

15

Details of Derivation…

16

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

18

Force Changes the Energy Landscape

Bustamante et al., Ann. Rev. Biochem. 2004