Structural Biology: Principles and Practice
The structure, dynamics, and energetics of biological systems can be investigated using biophysical techniques that involve the absorption, emission, and scattering of electromagnetic radiation and particles. This course provides a detailed overview of these structural biology approaches used for the study of macromolecules (particularly proteins and nucleic acids) so that students will be able to understand journal articles and seminars dealing with these methods, as well as recognize the potential application of the techniques to specific biochemical or molecular biological studies. Since critical interpretation of the measured parameters requires an understanding of the underlying principles, knowledge of the underlying physical basis of the methods with at least a qualitative grasp of the physical chemistry and relevant vocabulary is expected. Potential applications will be discussed with a focus on the kinds of information that can be learned from the techniques. Actual experimental issues and problems will be addressed. While many different techniques will be surveyed, the emphasis is on those techniques that enable atomic or near-atomic level descriptions of macromolecular structure: X-ray crystallography, NMR spectroscopy, and electron microscopy.
Topics covered include the theory and practice of optical spectroscopy in the study of conformations of proteins and nucleic acids; electron cryomicroscopy applied to macromolecular structure from 2D crystals and and unordered single particles; the physical principles and analytic uses of NMR spectroscopy in the study of protein structure, dynamics in the solution and solid states; X-ray diffraction on single crystals and its use as a tool in elucidating the three- dimensional fold of proteins, ligand binding sites and enzymatic mechanisms.
Course Next Offered
Course Time and Location
Room 4279, Medical Sciences Building
10-11am, Tuesdays and Thursdays
Method of Student Evaluation
Problem sets (take home): 30%
Midterm test (in class): 24%
Final exam (3 hours): 45%
“Biological Spectroscopy”, Ian D. Campbell & Raymond A. Dwek (Benjamin/Cummings Publishing Company, Inc., 1984)
“Biophysical Chemistry”, part II, Charles R. Cantor and Paul R. Schimmel (W.H. Freeman, 1980)
“Crystal Structure Analysis, a Primer”, 2nd ed., Jenny P. Glusker & Kenneth N. Trueblood (Oxford University Press, 1985)