SYLLABUS: PR 613, MACROMOLECULAR STRUCTURE

Monday, Wednesday, and Friday, 11 AM-noon, Bluemle 202

2 January – 21 March 2008

 

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, 11 AM-1 PM, and the final will be given on Friday, 21 March, 11 AM-1 PM, in Bluemle 202. All of the exams will emphasize problem-solving and original thinking, rather than memorization. You should work through the listed homework problems from the back of each chapter every week. These will be good experiences for the exams, and will contribute 20% of your grade. The midterm and final will each contribute 40% of your grade.

            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, Oxford University Press.

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

john.pascal@mail.jci.tju.edu

804 BLSB

3-4596

Dr. Quong

aquong@mail.jci.tju.edu

815 BLSB

3-5703

Dr. Williams

jwilliam@mail.jci.tju.edu

826 BLSB

3-4573

Dr. Wickstrom

eric@tesla.jci.tju.edu

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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