lecture 3/4 rob phillips california institute of technology (block et al.) (wuite et al.)

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

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

Lecture 3/4Lecture 3/4

Rob PhillipsCalifornia Institute of Technology

(Block et al.)

(Wuite et al.)

Page 2: Lecture 3/4 Rob Phillips California Institute of Technology (Block et al.) (Wuite et al.)

Reduced Description of Protein StructureReduced Description of Protein Structure

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

Single Molecule Experiments: A Single Molecule Experiments: A ReminderReminder

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.

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

DNA as a Case Study in Single DNA as a Case Study in Single Molecule BiomechanicsMolecule Biomechanics

Force-extension curves for DNA have served as a testbed for the quantitative analysis of the deformation of macromolecules.

(Lieber et al.)

(Lieber et al.)

Page 5: Lecture 3/4 Rob Phillips California Institute of Technology (Block et al.) (Wuite et al.)

Atomic Force Microscopy as a Atomic Force Microscopy as a Single Molecule ProbeSingle Molecule Probe

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.

(Fernandez et al.)

Page 6: Lecture 3/4 Rob Phillips California Institute of Technology (Block et al.) (Wuite et al.)

Single Molecule Experiments with Single Molecule Experiments with the AFMthe 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.

Page 7: Lecture 3/4 Rob Phillips California Institute of Technology (Block et al.) (Wuite et al.)

Muscle structureMuscle structure

Page 8: Lecture 3/4 Rob Phillips California Institute of Technology (Block et al.) (Wuite et al.)

Muscle structureMuscle structure

Page 9: Lecture 3/4 Rob Phillips California Institute of Technology (Block et al.) (Wuite et al.)

Viral Packing: Relevant Scales Viral Packing: Relevant Scales

Equilibrium entropic size of unpacked DNA:

Capsid size = 40nm

(Hendrix)

Persistence length of DNA, length over which DNA canbe thought of as being stiff.

There is a negative charge every .17nm of length along DNA – electrostatic energy crucial also.

Page 10: Lecture 3/4 Rob Phillips California Institute of Technology (Block et al.) (Wuite et al.)

E. Coli from LehningerE. Coli from Lehninger

Page 11: Lecture 3/4 Rob Phillips California Institute of Technology (Block et al.) (Wuite et al.)

DNA Force ExtensionDNA Force Extension

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