SYLLABUS: PR 613, MACROMOLECULAR STRUCTURE
Monday,
Wednesday, and Friday,
2
January –
Purpose: This problem-based course is designed
to train molecularly oriented students in the field of structural biology. Familiarity with physical chemistry is most
beneficial for understanding these lectures.
Objectives: We will study protein and nucleic
acid structure and function, focusing on energetic forces that guide folding,
and computer modeling to predict structures. To reveal protein and nucleic acid
structures we will study optical spectroscopy (absorbance, fluorescence,
circular dichroism), electrophoresis, mass spectroscopy, magnetic resonance
spectroscopy, X-ray crystallography, and sedimentation. We aim to develop your
critical, analytical and problem-solving abilities in structural biology.
Lectures on Monday and Friday will be supplemented by problem sessions or
hands-on experience on Wednesdays, in the classroom, laboratories, or offices.
Tasks: The PR613 midterm (examples of the 2003, 2001, and 1999 midterms) will be
given on Friday, 15 February,
Required text: Tinoco, Ignacio, Jr., Sauer, Kenneth, Wang, James C., &
Puglisi, Joseph D. (2001) Physical Chemistry: Principles and Applications in
Biological Sciences, 4th ed. Prentice Hall, ISBN: 0-13-095943-X (in our
bookstore)
Recommended general reference books:
van
Holde, Kensal E., Johnson, W. Curtis, & Ho, Pui Shing (1998) Principles
of Physical Biochemistry. Prentice Hall. ISBN 0-13-720459-0
Cantor,
Charles, and Schimmel, Paul (1980) Biophysical Chemistry, Vols. I-III,
W. H. Freeman and company, San Francisco, 0-7167-1188-5, 0-7167-1192-3, QU 4 C232b 1980.
Recommended reference books for crystallography:
Drenth, Jan (1994) Principles of Protein X-Ray Crystallography,
Springer-Verlag, QU
55 D772P 1994.
Rhodes, Gale (2006) Crystallography Made Crystal Clear, 3rd
Ed., Academic Press, 0-1258-7073-6
Recommended reference books for mass spectroscopy:
Kinter,
M. & Sherman, N. E. (2000) Protein Sequencing and Identification Using
Tandem Mass Spectrometry, Wiley-Interscience.
Chapman,
J. R. Ed. (2000) Mass Spectrometry of Proteins and Peptides, Humana Press,
QU 55 M414 2000.
Recommended reference books for nuclear magnetic resonance
spectroscopy:
Cavanagh,
J., Fairbrother, W.J., Palmer III, A.G. and Skelton, N. J. (1996) Protein
NMR Spectroscopy: Principles and Practice, Academic Press, QD 96 .N8 P967
1996.
Evans,
J. N. S. (1995) Biomolecular NMR Spectroscopy,
Recommended reference books for sedimentation: Hansen,
J. C., and Cole, J. L. (1999) Analytical Ultracentrifugation as a Contemporary
Biomolecular Research Tool. Journal of Biomolecular Techniques 10(4,
December):163-176. (pdf on course website)
The attached schedule gives the
date, topic, chapter, and lecturer for each session. The lectures will be supplemented with some hands-on-experience.
Please contact any of the lecturers below should the need arise. They are
always available for questions. Remember, there is no such thing as a dumb
question!
|
Dr. Pascal |
804 BLSB |
3-4596 |
|
|
Dr. Quong |
aquong@mail.jci.tju.edu |
815 BLSB |
3-5703 |
|
Dr. Williams |
826 BLSB |
3-4573 |
|
|
Dr.
Wickstrom |
219
BLSB |
5-4578 |
|
Lecture No. |
PR
613 Lecture Topic |
Chapter |
Problem |
Lecturer |
|
1. 2 January |
Hands-on assembly of amino acid and nucleotide dimer CPK models. |
9 |
|
Wickstrom |
|
2. 4 January |
Primary and secondary structures of proteins and nucleic acids;
hydrogen bonding, ionic and hydrophobic interactions. See http://tesla.jci.tju.edu/pics/aant. |
9 |
18, 23 |
Wickstrom |
|
3. 7 January |
Optical spectroscopy: photons, chromophores, transition dipole
moments, absorbance, and concentration. See http://tesla.jci.tju.edu/abs. |
10 |
4, 7 |
Wickstrom |
|
4. 9 January |
Absorbance spectrum and melting of a protein, Bluemle 219 |
9,10 |
|
Wickstrom |
|
5. 11 January |
Optical spectroscopy: circular dichroism: molecular chirality,
structural transitions of macromolecules, and analysis of spectral results.
See http://tesla.jci.tju.edu/cd. Turn in homework. |
10 |
|
Wickstrom |
|
6. 14 January |
Optical spectroscopy – fluorescence: dependence on changes in
environment around a single residue, ligand binding, measurement of
individual fluorescent cells, and cell sorting. See http://tesla.jci.tju.edu/fluor. |
10 |
15 |
Wickstrom |
|
7. 16 January |
Circular dichroic spectrum and melting of a protein, Bluemle 822 |
10 |
|
Wickstrom |
|
8. 18 January |
Optical spectroscopy – radiation: radioactive decay, particle detection,
liquid scintillation, surface plasmon resonance. See http://tesla.jci.tju.edu/rad. |
10 |
9 |
Wickstrom |
|
9. 21 January |
Particles in a field: mass spectroscopy, electrophoresis, and sedimentation.
See http://tesla.jci.tju.edu/field. |
6 |
14, 16 |
Wickstrom |
|
10. 23 January |
Hands-on or problem-solving session |
11 |
|
Wickstrom |
|
11. 25 January |
Thermodynamics of macromolecular transitions. See http://tesla.jci.tju.edu/thermo. Turn
in homework. |
10 |
20 |
Wickstrom |
|
12. 28 January |
Mass spectroscopy: application to complex proteins. |
6 |
|
Quong |
|
13. 30 January |
Hands-on mass spectroscopy computer session in Bluemle 809 |
6 |
|
Quong |
|
14. 1 February |
Diffraction: overview, crystallization. |
12 |
|
Williams |
|
15. 4 February |
Diffraction Theory: wave/vector math and scattering. |
12 |
|
Williams |
|
16. 6 February |
Diffraction Theory: scattering from a periodic lattice,
reciprocal space, and symmetry. |
12 |
|
Williams |
|
17. 8 February |
Diffraction Theory: phase problem, Patterson functions, and
molecular replacement. Turn in homework. |
12 |
|
Williams |
|
18. 11 February |
Diffraction Theory: multiwavelength anomalous diffraction and
crystallographic statistics. |
12 |
|
Williams |
|
19. 13 February |
Laboratory: crystallization of a protein. |
12 |
|
Williams |
|
20. 15 February |
MIDTERM
EXAM |
1,2,3,6,9,10,11,12 |
|
Wickstrom |
|
21. 18 February |
Diffraction Theory: model building and refinement. |
12 |
|
Williams |
|
22. 20 February |
Laboratory: model building and refinement. |
12 |
|
Williams |
|
23. 22 February |
Crystallography: quality of structure. Turn in homework. |
12 |
|
Williams |
|
24. 25 February |
Laboratory: validation of structure. |
12 |
|
Williams |
|
25. 27 February |
Nuclear magnetic resonance: overview and practical aspects. |
12 |
|
Williams |
|
26. 29 February |
Nuclear magnetic resonance: nuclear spin and
coupling interactions. See http://tesla.jci.tju.edu/nmr. |
10 |
|
Williams |
|
27. 3 March |
Nuclear magnetic resonance: measurement and multi-dimensional
experiments. See http://tesla.jci.tju.edu/nmr. |
10 |
|
Williams |
|
28. 5 March |
Nuclear magnetic resonance: more multi-dimensional experiments. |
10 |
|
Williams |
|
29. 7 March |
Nuclear magnetic resonance: Determination of protein and nucleic
acid structures. See http://tesla.jci.tju.edu/nmr. Turn in homework. |
10 |
|
Williams |
|
30. 10 March |
Nuclear magnetic resonance: solid state, dynamics,
structure-activity relationships, and electrostatics. |
10 |
|
Williams |
|
31. 12 March |
Nuclear magnetic resonance: practical aspects of
structural methods. |
10,12 |
|
Williams |
|
32. 14 March |
Size and shape of
macromolecules determined by analytical sedimentation (XLA). See pdf on
Banner. |
6 |
|
Pascal |
|
33. 17 March |
Gel filtration analysis of
ligand binding association equilibria and kinetics. |
6 |
|
Pascal |
|
34. 19 March |
Review
and problem-solving session |
6,10,12 |
|
Williams |
|
35. 21 March |
FINAL EXAM |
6,10,12 |
|
Wickstrom |
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