Proteins and Molecular Mechanisms -BCH 455/555
Fall 2006 Tues. and Thurs. 11:45-1:00
Room 158 Weaver Labs

Prerequisites: BCH451: Principles of Biochemistry, BCH453: Biochemistry of Gene Expression.

Text book: Proteins: Structures and Molecular Properties Thomas E. Creighton, second edition (1993)

Supplemental text: on reserve at the library
Protein structure and function
Gregory A Petsko and Dagmar Ringe
New Science Press (2004)

Extra readings: on E-reserve through the NCSU library

Creighton is an excellent text, but because it is over ten years old it is somewhat dated in places. A number of extra readings from the supplementary text (Protein structure and function) have been chosen to address this. This text is a good resource for further readings on many of the topics during the semester. Other readings have been added to give more background or more detail on a topic. The readings in Part III: Case studies - protein function and disease (see syllabus) are papers from the literature. The graduate students will be reading these papers. Undergraduates are encouraged to read some of these papers, though they may be difficult to read if you are not used to reading the literature.

All of the readings will be on E-reserve through the NCSU library. To access the E-reserve material, open the NCSU library web page ( http://www.lib.ncsu.edu ). You will see a link to "Course and E-reserves" listed in the top left corner under "services". It might take the library a few days to post all of the readings. The articles can also be found through the library electronic journals.

Molecular Models:

We will use molecular models to build amino acids and protein structures. I will provide models for groups to share. If you want to purchase your own models, you can do so directly from the company Molecular Visions at www.molecularvisions.com/cat--Molecular-Model-Kits--kits.html. They sell the Darling Models. You can purchase the Biochemistry kit for $31.

Groups and class activities:

Lectures will be interspersed with class activities to stimlate active participation in learning instead of passive reception of "facts". Generally bring calculators to class, if you have them, since activities may include solving problems.

The class will be divided into groups of three for class activities and various homework assignments. Groups are meant to:
- allow students to learn from each other
- stimulate discussion and class participation.
- provide a forum for active learning to supplement lectures
Working in groups has been shown to improve learning for all levels of students.

I will assign the groups. Group members will not necessarily be your close friends. You will be expected to participate as a responsible group member. Throughout the semester you will be asked to evaluate how your group is working. If someone is not contributing as a responsible group member, they will be asked to leave the group and will be expected to carry out the assignments on their own. Half way through the semester we will evaluate the groups.

Each group will be responsible for answering questions for one of the homework assignments during the semester (see below).

Grading:
Undergraduate students:

 5% class participation
This includes working in groups during class, participating in presentations by groups, contributing to class discussions, and group evaluations.

 25% homework
In general, homework will be assigned on Tuesday and will be due the next Tuesday. Late homework will be accepted on the Thursday during class after it's due, but no later. I will choose one assigned problems at random to grade. Each week one of the groups will be responsible to answer questions about the returned problem sets.

Grading for each assignment - 80% for thought, 20% for the right answer.

I will grade the homework primarily on how you thought about a problem, and not primarily for the right answer. Therefore you must show your work or communicate how you approach the problems in order to get full credit. You are encouraged to work in groups. The homework is for your benefit, so please be sure you understand it and answer the questions yourself. Each individual must hand in their own homework, even if you work in a group. If 2 people hand in the same answers, I don't know who did the thinking. I will therefore give you a 0 for thought. So answer the problems in your own words.

There will be one longer homework assignment after week 16. This assignment is designed to get you using some of the powerful database searches and prediction algorithms available. For this assignment, you will be given the sequence of an unknown protein and will be asked to predict something about the structure and function of the protein.

70% tests

There will be 2 in-class exams and one comprehensive final exam given during final exam week. The in-class exams will each be worth 20% of your grade, and the final will be worth 30%.

Test 1: T. Sept. 26 11:45-1:00
Test 2: Th. Nov. 2 11:45-1:00
Final Exam: Dec. 12 8-11 am

Exceptions to the grading rules (unfinished homework assignments or missed exams) require prior communication with me and official, university-accepted, written documentation. Please see http://www.ncsu.edu/provost/academic_regulations/attend/reg.htm for information about excused absences.

Graduate students:

 10% presentation
Graduate students will contribute a 15 minute presentation one time during the semester summarizing one of the assigned supplementary readings, or a mutually agreed on, relavant reading of your own choosing.

5% class participation
15% homework
70% tests

The following grade scale will be used:

Grading Scale

Undergraduates BCH455		Graduate Students BCH555
91-100%	A+	95-100%
81-90%	A	84-94%
80%	A-	83%
78-79%	B+	81-82%
68-77%	B	71-80%
67%	B-	70%
65-66%	C+	68-69%
58-64%	C	61-67%
57%	C-	60%
56%	D+	59%
51-55%	D	56-58%
50%	D-	55%
<50%	F	<55%

WebCT:

WebCTVista will be used to post the course syllabus, course notes, some important calendar dates, and e-mail. All registered students for the course should have access to the course WebCTVista site. The url for Vista is: http://vista.ncsu.edu . To login, use your Unity ID and Unity Password. If you have problems logging in to WebCT or using WebCT, contact the WebCT Help Desk at 515-HELP, e-mail help@ncsu.edu, or check out the online help at http://vista.ncsu.edu/index.php .

Overall Objectives :

1) To appreciate the chemical, thermodynamic and structural properties of proteins and how they contribute to protein function.

2) Introduce some of the major areas of research in protein science today.

3) Introduce how the ever-growing database of protein sequences and structures is revolutionizing our understanding of evolution, protein folding, protein function, and how we do science. Start you using database tools.

4) Develop the foundation for you to read the scientific literature.

5) Introduce how protein science is being used to affect disease.

6) Understand and learn to consider how we know . Facts always contain a degree of interpretation. Knowing how we know allows you to consider what we don't know, and to make new discoveries.

7) Use the history of protein science to appreciate the foundation of the subject and the seminal discoveries and ideas. History provides a perspective on how ideas change and how discoveries are made, and how recent our current understanding is. Finally it demonstrates how individuals have contributed to science, and how you might contribute.

Supplementary Readings

1. Rhodes, G., Crystallography Made Crystal Clear . 2000, Academic Press: San Diego, CA. p. 153-186.

2. Spronk, C.A., S.B. Nabuurs, A.M. Bonvin, E. Krieger, G.W. Vuister, and G. Vriend, The precision of NMR structure ensembles revisited. J Biomol NMR, 2003. 25 (3): p. 225-34.

3. Cooper, A., Thermodynamics of protein folding and stability. 1999.

4. Petsko, G. and D. Ringe, Protein structure and function , in Primers in Biology . 2004, New Science Press Ltd: London. p. 130-147.

5. Petsko, G. and D. Ringe, Protein structure and function , in Primers in Biology . 2004, New Science Press Ltd: London. p. 40-45.

6. Tong, L., S. Pav, D.M. White, S. Rogers, K.M. Crane, C.L. Cywin, M.L. Brown, and C.A. Pargellis, A highly specific inhibitor of human p38 MAP kinase binds in the ATP pocket. Nat Struct Biol, 1997. 4 (4): p. 311-6.

7. Reiling, K.K., N.F. Endres, D.S. Dauber, C.S. Craik, and R.M. Stroud, Anisotropic dynamics of the JE-2147-HIV protease complex: drug resistance and thermodynamic binding mode examined in a 1.09 A structure. Biochemistry, 2002. 41 (14): p. 4582-94.

8. Grimsby, J., R. Sarabu, W.L. Corbett, N.E. Haynes, F.T. Bizzarro, J.W. Coffey, K.R. Guertin, D.W. Hilliard, R.F. Kester, P.E. Mahaney, L. Marcus, L. Qi, C.L. Spence, J. Tengi, M.A. Magnuson, C.A. Chu, M.T. Dvorozniak, F.M. Matschinsky, and J.F. Grippo, Allosteric activators of glucokinase: potential role in diabetes therapy. Science, 2003. 301 (5631): p. 370-3.