Physics 303/607

Biology 303/607

Class times: MWF 10-10:50 AM

Instructors:

(1) Professor Jed Macosko, Phone: 758-4981, Office: 302 Olin, e-mail:macoskojc@wfu.edu, http://www.wfu.edu/~macoskojc/

(2) Professor Daniel Kim-Shapiro, Phone: 758-4993, Office: 208 Olin, e-mail:shapiro@wfu.edu, http://www.wfu.edu/~shapiro/

Office hours: Mondays and Wednesdays 2-4 pm, or by appointment.

Texts: Principles of Physical Biochemistry, 2nd Edition, by K.E. van Holde, W. C. Johnson, and P.S. Ho; Neurodynamix,by W.O. Friesen and J.A. Friesen. Additional reading will be assigned in the form of journal articles and handouts

Supplementary texts: 1. Biophysical Chemistry Part II, Techniques for the study of biological structure and function, by Charles Cantor and Paul Schimmel (1980). 2. Biochemistry by Lupert Stryer (1988).

Grading:

Undergraduate Students

2 hour exams.............................................................40%

Project..................................................................10%

Final Exam................................................................30 %

Problem Sets............................................................20%

Graduate Students

2 hour exams.............................................................30%

Project..................................................................10%

Presentation of Journal Article......................................10%

Final Exam................................................................30 %

Problem Sets............................................................20%

Emphasis in grading will be placed on how each problem is solved. All work showing how the solution was obtained must be shown. An answer with the correct answer but poor method is inferior to one with the wrong answer but good method.

Problem sets will generally be assigned on a weekly basis and the students will have one week to complete them. Students may help each other on problem sets but each student must write their own solution to each problem. The project that all students do will be a 5-10 page paper focusing on a particular topic in biophysics. The project could be a service learning project (see instructors for more information on that).

Graduate students will present one of the journal articles that are part of the reading assignments.

Exam Schedule

Hour Exams: February 26, April 21; Final Exam: April 30 (2 PM)

Click here to look at the x-ray scattering from linear arrays of atoms onto a cylindical screen. (This was developed by Ching-Wan Yip and Yue Ling Wong).

X-Ray Diffraction sites: An Introduction to the Scope, Potential and Applications of X-ray Analysis , Elementary X-Ray Diffraction for Biologists.

Other sites: ExPASy Molecular Biology Server: The ExPASy (Expert Protein Analysis System) You will probably want to download Swiss-PdbViewer - it is really cool. Go through Swiss Model under Tools and Software Packages.


Biophysics Syllabus

 

Date
Topic
Lecture notes
HW
Reading
Jan. 13 & 15
Introduction-1: Structures biological macromolecules, mainly proteins, DNA and RNA
van Holde, Ch. 1
Jan. 20 & 22
Introduction-2: Molecular interactions in biological macromolecules HW-2, see lecture notes
van Holde Ch. 3.1 - 3.3

 

Part I Biophysical Methods

  1. Introduction (Macosko)
    1. Biological Macromolecules (mainly proteins, DNA and RNA, molecular interactions, overview of thermodynamics
      Reading: van Holde, chapters 1-4 (partial).

HW 1: (book, see lecture notes)

  1. X-ray diffraction, DNA/RNA Structure (Macosko)

1. Overview, 2. Detailed lecture

Bragg's law, von Laue conditions, reciprocal space, Fourier Transforms, electron density r(r) & Structure factor F(hkl), phase problem, Patterson maps, fiber (DNA) diffraction , History of Watson, Crick, Franklin & Wilkin's discoveries (two movies)

Reading: van Holde chapter 6, and the following papers:

April 25, 1953 papers: Watson and Crick Paper 1, Wilkins paper, Franklin paper 1,

Later 1953 papers: Watson Crick Paper 2, Franklin paper 2

HW 3: (see lecture notes)

 

  1. Light Scattering, Sedimenation, Gel Electrophoresis, Higher Order DNA Structure, Scattering supplement, Polarization in light scattering (Kim-Shapiro)

math supplement

Sedimenation, mass spectrometry, Gel electrophoresis (Fick's Law), Light Scattering (Classical, Dynamic, Polarized)

DNA Topology (Length, Twist, and Writhe), Chromosome Structure

Reading: van Holde, chapters 5 and 7, Shapiro et al: Polarized Light Scattering

Additional Papers:

Wang et al: Helical repeat in DNA solution

Dorigo et al: Nucleosome Arrays Reveal theTwo-Start Organization of the Chromatin Fiber

Mohd et al: Perspective chromatin

Francis et al: Chromatin Compaction by a Polycomb Group Protein Complex (with perspective above)

HW 6 (separation) Maple program for gel-1, Maple program for gel-2 and Explanation for maple program for gel-2

HW 7 (Light scattering)

  1. Absorption Spectroscopy, Protein Structure (Kim-Shapiro)

UV, VIS spectroscopy, linear and circular dichroism

Protein primary, secondary, tertiary, quaternary structure

Reading: van Holde chapters 8-10

Addtional papers:

Hofrichter et al: Nanosecond absorption spectroscopy of hemoglobin: Elementary processes in kinetic cooperativity

Goldbeck et al: Multiple pathways on a protein-folding energy landscape: Kinetic evidence

Monod Wyman and Changeux On the Nature of Allosteric Transitions:A Plausible Model

HW 6 (absorption)

  1. Emmission Spectroscopy (Macosko)

Fluorescence (phenomenon), Fluorescence microscopy, native fluorophores in proteins, solvent effects, Quantum yield, fluorescence decay, FRET (resonance energy transfer), linear polarization of fluorescence and emissin anisotropy, Perrin plots.

Reading: van Holde, Chapter 11

Papers:

Ha et al (1): Single molecule FRET (early, basic, using SNOM) (also single molecule)

Ha et al (2): Single molecule FRET (RNA conformation) (also single molecule)

Raney et al: Detecting helicase by fluorescence

HW 7: van Holde 11.2 to 11.7

  1. Single Molecule biophysics (Macosko)

Single molecule vs. bulk experiments, Atomic Force Microscopy (imaging and manipulating), laser tweezers, single molecule fluorescence

Reading: Handout

Papers:

Liphardt et al: Single molecule RNA folding (laser trap)

Davenport et al: Observing a single RNA polymerase transribing (laser tweezer and pipette)

Schwesinger et al: AFM Force spectroscopy, relation between force and off rate

Guthold et al: AFM observing a single RNA molecule transcribing

Lu et al: Single molecule enzyme dynamics (single molecule fluorescence)

Bokinsky et al: Single molecule FRET of RNA unfolding

Tskhovrebeva et al Single molecule Titin stretching with laser tweezer

HW 8: (see lecture notes).

 

  1. Electron Paramagnetic Resonance, Protein Function - Hemoglobin (Kim-Shapiro)

Electron Paramagnetic Resonance, Hemoglobin cooperativity Studies using EPR and time-resolved absorption spectroscopy

Reading: Handout

Paper:

Yonetani et al: NO hemoglobin

Part II Membrane Biophysics

  1. Biological membranes and Transport (Kim-Shapiro)

Description of membranes, Diffusion, Facilitated transport, Nernst Equation, Donnan Equilibrium

Reading: van Holde chapters 13-14

  1. Nerve Excitation (Kim-Shapiro)

Neurons, Action Potential, Propagation of action potential, measurements in membrane biophysics, Synaptic transmission

Reading: Frisens Sections 1 and 2