Syllabus Advanced Biophysics

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Description/Objectives

Biophysics involves the application of physical techniques to achieve an understanding of life processes at a molecular level. Physical techniques are central to the measurement of the atomic structure, dynamics and interactions of molecules that are a core foundation of modern molecular biology, while physical theory governs the predicted behavior of biomolecules and helps us achieve a mechanistic understanding of how they work. Thus, biophysics is a central science in the fundamentals of normal physiology, molecular pathology, and in the development of pharmaceutical remedies for a wide range of diseases.

This is the second of two primarily lecture courses that will prepare graduate and advanced undergraduates for research and technical work in Molecular Biophysics. It will cover the practical aspects of the elucidation of macromolecular structure and dynamics by NMR spectroscopy and x-ray crystallography, and the characterization of macromolecular interactions by electron microscopy, mass spectrometry and fluoresence methods. It will examine computational methods for interpreting structure, predicting properties and simulating mechanisms of action.

At the conclusion of this course, students will have a working understanding of the primary experimental and computational methods by which the structure, dynamics and interactions of biomolecules are elucidated and their actions simulated. Students will be able to critically assess primary research literature written for a general scientific audience that uses any of the common physical approaches to understand macromolecular systems. Students will understand the nature of advances that can be made with the principal techniques and their limitations. They will also be prepared for mentored practical research investigations that use the primary methods.

Registration

OHSU PSU
Course number BMB 6xx CH 510 (Sp. Topics/Biophysics; ID to be replaced soon.)
Credit hours 3 3
Offered Spring 2011 & annually thereafter

Requirements

Introductory Biophysics or consent of the course directors.

Instructors

The course will be team-taught by faculty from Portland State University and Oregon Health & Science University.

Course Directors

OHSU PSU
Michael S. Chapman, Ph.D. David H. Peyton, Ph.D.
E-mail mailto:chapmami@ohsu.edu mailto:peytond@pdx.edu
Office hours Mon noon-1pm; Wed 2-3pm: MRB 534A TBA: 323B SB1
Web URL http://xtal.ohsu.edu/ http://web.pdx.edu/~peytond/
Phone (503) 494-1025 (503) 725-3875

Topics / Calendar

  1. Avanced Magnetic Resonance :
    1. Methods of Biomolecular Structure Determination
    2. Probing the dynamics of macromolecules
    3. Special topics: Paramagnetic NMR & ESR, spin labeling & Solid-state NMR
  2. Visible & Electron Microscopy
    1. Theory of Light Microscopy
    2. Fluorescence, Confocal & Correlative Microscopy
    3. Transmission EM - theory
    4. Biological samples
    5. 3D reconstruction
  3. Practical Crystallography
    1. Crystallization
    2. Data collection
    3. Phasing by molecular replacement
    4. Model-building & Refinement
  4. Interpretation of Structure
    1. Databases & their use
    2. Homology modeling
    3. Docking
    4. Electrostatics - Potentials & pKs
  5. Molecular Dynamics
    1. Simulated annealing
    2. Normal modes
    3. Accelerated methods / enhanced sampling
  6. Mass spectrometry in biomolecular structure / interactions
    1. Footprinting
    2. Dynamics
  7. Single Molecule Methods
    1. Fluorescence
    2. Atomic Force Microscopy
    3. Surface Plasmon Resonance
    • Case Studies:
      • Molecular Motors
      • Protein Mis-folding & Disease

Schedule for Advanced Biophysics

Materials

Recommended Text

Principles of Physical Biochemistry (2nd Ed.) by van Holde, K.E., Johnon, C. & Ho, P.S. (2006) Prentice Hall, ISBN-10: 0130464279 / ISBN-13: 9780130464279

Web resources

Lecture notes

In-class presentations will be posted at the discretion of the instructor following class with links from Schedule.

Evaluation

There will be two mid-terms and a final examination that will contribute 20%, 30% and 50% respectively to the overall assessment.