Lecture 3/4

1. Rob Phillips California Institute of Technology Lecture 3/4 (Block et al.) (Wuite et al.)

2. Reduced Description of Protein Structure

3. Single Molecule Experiments: A Reminder • There are a variety of techniques for measuring the relation between force and extension for single molecules. This domain has been dubbed dynamical force spectroscopy.

4. DNA as a Case Study in Single Molecule Biomechanics (Lieber et al.) • Force-extension curves for DNA have served as a testbed for the quantitative analysis of the deformation of macromolecules. (Lieber et al.)

5. Atomic Force Microscopy as a Single Molecule Probe (Fernandez et al.) • Atomic force microscopy provides a complementary way of measuring the action of the molecules of life when subjected to force. • Single molecule analog of the Instron machine. • Dynamical Force Spectroscopy – each molecule has its own force/extension signature.

6. Single Molecule Experiments with the AFM (Fernandez et al.) Concrete example of dynamical force spectroscopy in the case of the giant muscle protein titin. Key modeling challenge: the precise details of the force/extension curve. Note that by performing mutations on the titin molecule, the force/extension signature can be altered.

7. Muscle structure

8. Muscle structure

9. Viral Packing: Relevant Scales Capsid size = 40nm (Hendrix) Persistence length of DNA, length over which DNA can be thought of as being stiff. Equilibrium entropic size of unpacked DNA: There is a negative charge every .17nm of length along DNA – electrostatic energy crucial also.

10. E. Coli from Lehninger

11. DNA Force Extension