C581: Function & Structure of Macromolecules

Fall 1997


Instructors: Prof. Martin Stone Prof. Martha Oakley
Location: Chemistry Room A508 Chemistry Room A704
Email: mastone@indiana.edu oakley@indiana.edu
Phone: 855-6779 855-4843

Date Meeting Subject Reading
Proteins - Part I: Protein Structure And Stability
Sept. 1 1 Introduction, primary structure, detection, and separation§1.1-1.7
Sept. 3 2 Important physical chemistry - a conceptual approach §8.2
Sept. 5 3 Conformation and secondary structure §5
Sept. 8 4 3D structure of proteins - in A400 §6.2
Sept. 10 5 Non-covalent interactions and stabilization of structure§4
Sept. 12 6 Sequence searching, alignment, and homology modeling - A400-
Proteins - Part II: Methods For Studying Proteins
Sept. 15 7 Molecular modeling - A400 -
Sept. 17 8 X-ray crystallography - W.S. -
Sept. 19 9 X-ray crystallography - W.S. -
Sept. 22 10 X-ray crystallography - W.S. -
Sept. 24 11 NMR spectroscopy §6.3
Sept. 26 12 Introduction to DNA manipulation - M.O. -
Sept. 29 13 Synthesis and biosynthesis §1.8, 2.1-2.2
Oct. 1 14 Mutagenesis -
Oct. 3 15 Covalent modification, cross-linking, disulfide mapping>/td>§1.3, 2.3-2.4
Oct. 6 16 Protein-ligand interaction §8.2-8.4
Oct. 8 17 PROTEINS MIDTERM EXAM
Proteins - Part III: Special Topics
Oct. 1 18 Enzymes §9
Oct. 13 19 Protein folding §7.4-7.5
Oct. 15 20 Membrane proteins and receptors - in A400 §7.2
Oct. 17 21 G-protein mediated signal transduction -
Oct. 20 22 Tyrosine kinase mediated signal transduction -
Oct. 22 23 Structures of some proteins - in A400 -
Oct. 24 24 Structures of some proteins - in A400 -
Nucleic Acids - Part I: Introduction and Nucleic Acid Structure
Oct. 27 25 DNA Synthesis
Oct. 29 26 DNA Sequencing & Chemical Modifications
Oct. 31 27 DNA & RNA Structure: A, B, Z-Form Helices
Nov. 3 28 Triplexes, G-Quartets & Holliday Junctions
Nov. 5 29 tRNA Structure; Ribosomal RNAs
Nucleic Acids - Part II: Catalytic RNA
Nov. 7 30 Hydrolysis; Intro to Ribozymes
Nov. 10 31 Group I Intron: Intro & Catalytic Mechanism
Nov. 12 32 Group I Intron: Structure Prediction & RNA Folding
Nov. 14 33 Hammerhead & RNase P
Nucleic Acids - Part III: Small Molecules That Bind to Nucleic Acids
Nov. 17 34 DNA-Binding Natural Products
Nov. 19 35 Minor-Groove Binding Molecules
Nov. 21 36 Minor-Groove Binding Molecules
Nucleic Acids - Part IV: Nucleic Acid Binding Proteins
Nov. 24 37 DNA Binding Proteins: Intro and HTH Motif
Nov. 26 - Thanksgiving Recess - class does not meet
Nov. 28 - Thanksgiving Recess - class does not meet
Dec. 13 38 DNA Binding Proteins: Helix-Turn-Helix Motif
Dec. 33 39 DNA Binding Proteins: HTH and DNA Bending
Dec. 5 40 DNA Binding Proteins: Zinc Finger Motif
Dec. 8 41 DNA Binding Proteins: Zinc Finger Libraries
Dec. 10 42 RNA Binding Proteins: Rev
Dec. 12 43 RNA Binding Proteins: RNP Domains


C581 Web Site

The class web site at http://www.molvis.indiana.edu/C581_F97 will include a copy of the syllabus, instructions for modeling workshops and assignments, and forms to register for the modeling workshop and pet protein assignment.


Reading:

Proteins: The sections indicated above are in the text book "Proteins: Structures and Molecular Properties" by T.E. Creighton, Freeman 2nd ed., 1993. Everyone should get a copy of this book. The sections covered in class are clearly not in the same order as in the text. However, this course will cover most of the topics discussed in Chapters 1, 2, 4, 5, 6, 7, 8, and 9 of Creighton (Chapters 3 and 10 will not be covered).
Some structures shown in class will be from the book "Introduction to Protein Structure" by C. Branden and J. Tooze which is on reserve in the chemistry library. It is not necessary to purchase this book.
In addition, sections of several lectures will be based on primary literature references. Copies of these papers will be plaed on reserve in the Chemistry and Biology libraries. You will be expected to read these papers and understand them in detail.

Nucleic Acids: There is no single required text for this half of the course. Nonetheless, assigned readings will play a major role in this course. These readings will be taken largely from the following texts:

These books, or copies of the relevant chapters, can be found on reserve in the biology and chemistry libraries. Relevant review articles and primary literature will also be placed on reserve in both libraries.


Grades

The grade for this course will be broken down as follows:
Pet Protein Project 20%
Proteins Midterm Exam 10%
Proteins Final Exam 20%
Proteins Total 50%


Nucleic Acids Problem Sets 5%
Nucleic Acids Midterm Exam 10%
Nucleic Acids Term Paper 15%
Nucleic Acids Final Exam 20%
Nucleic Acids Total 50%

Exam Dates, Times and Locations:

Proteins Midterm Exam (Lectures 1-16) Wed. October 8, 9.05-9.55 (in class time), BH003
Proteins Final Exam Wed. October 29, 7-9 pm, C122
Nucleic Acids Midterm Exam (Part I,II) Wed. November 19, 7-9 p.m., C122
Nucleic Acids Final Exam Wed. December 17, 8-10 a.m.

Other Important Dates:

Molecular Graphics Workshop Tuesday Sept. 9 or Thursday Sept. 11
Choose Pet Protein by: Monday Sept. 8
Pet Protein Asst. Step 2 Monday Sept. 15 (recommended)
Pet Protein Asst. Step 3 Monday Sept. 29 (recommended)
Pet Protein Asst. Due Wednesday Oct. 22, in class
Nucleic Acids Problem Set 1 Due Friday Nov. 7, 9 AM
Nucleic Acids Problem Set 2 Due Monday Nov. 17, 9 AM
Nucleic Acids Problem Set 3 Due Monday Nov. 24, 9 AM
Nucleic Acids Term Paper Due Monday, Dec. 8, 9 AM
Nucleic Acids Problem Set 4 Due Friday Dec. 12, 9 AM

Molecular Graphics Workshop:

A workshop aimed at learning to use the Insight II molecular graphics package for viewing protein molecules will be held on Tuesday Sept. 9 and Thursday Sept. 11. Each student will be required to attend for 1.5 h during one of the time slots shown on the web page. You should reserve a time using the web site. There is a maximum of 6 students per time slot (there are only 6 computers) so book early to get the slot you want. Note that Sept. 10 is a cume day for Chem. Dept. students so they may prefer to book the Thursday times. This workshop will not count towards your grade. However, it is compulsory to attend and you will need the skills learned for later graded exercises.

Click here for workshop instructions.

Pet Protein Assignment (20%)

The purpose of this assignment is to familiarize you with the structure and function of a particular protein and with methods for finding and aligning similar protein sequences and visualizing protein structures.
Step 1 (choosing the protein) must be completed by Sept. 8. Steps 2-4 should be submitted together no later than October 22. However, it will be easier and more educational if you distribute the work load according to the suggested completion dates below.
All sections of the assignment should be written in clear concise English and organized carefully so as to convey the greatest amount of meaning to the reader using the smallest number of words. The lengths of the sections given below are maximum lengths. You will lose points if you exceed these.

Step 1: Choose a Pet Protein - Deadline: Sept. 8
Choose a small protein that is of interest to you. It should be less than 250 amino acids to make the remainder of this project more practical - smaller than ~150 aa would be even better. Note that your choice should be for a specific protein from a specific organism (e.g. human interleukin-8) and the 3D structure must be available in the PDB. It should not be a protein that you are working on in the lab. It must be different from the proteins that other class members have chosen (not the same protein from a different organism). See the C581 PDB Directory for a list of proteins that others have chosen. Register your choice on the class web page no later than Sept. 8 (just the protein name, not the organism name).

Step 2: Description of the Protein Function - Suggested completion date: Sept. 15
Include in your assignment:
(a) The name of your protein, the name of the PDB file, and the protein sequence.
(b) A one page description of the biological and biochemical function of your pet protein.

Step 3: Sequence Searching and Alignment - Suggested completion date: Sept. 29
Do a protein sequence search and identify a group of proteins with varying degrees of sequence similarity to your protein. Align the sequences. The proteins you find should include: 2-3 with very similar sequences to your protein (e.g. they may be the same protein from a different species or a very similar protein from the same species); 2-3 with moderately similar sequences (e.g. they may be members of the same protein superfamily); and 2-3 with only slight similarity (e.g. proteins that you would not have guessed would be similar but whose similarity you can rationalize). Include in your assignment:

Step 4: Structure and Function - Deadline: Oct. 22
Examine your protein using InsightII and read any papers you think are important about the structure and structure-function relationships of your protein. Include in your assignment:

Step 5: Oral Presentation - Deadline Oct. 22
Be prepared to make a 5 minute oral presentation to the class describing the structure and structure-function relationships of your protein. You should prepare 1-2 .psv folders with informative graphics representations. You may also use 1-2 overheads. I will call on people in class (in A400) on Oct 22 and 24 to make these presentations. Note that not everyone will end up doing one.

Grades for Pet Protein Project
The 20% grade will be broken down as follows:
3%: Description of protein function
6%: Alignment and comparison with similar proteins
5%: Description of structure and structure-function relationships
3%: Graphics representation
3%: Writing style and organization

See also the Gallery of Protein Projects


Exams, Problem Sets, and Papers

Proteins Midterm Exam (10%): A one-hour midterm will be held in class time on Wednesday October 8 (rooms to be announced). This will include all topics that have been covered in class up until that time.

Proteins Final Exam (20%): A two-hour final will be held on Wednesday, October 29 at 7-9 pm (rooms to be announced). This exam will cover the entire proteins portion of the course.

Nucleic Acids Problem Sets (5%): You will be assigned a series of short molecular modeling tutorials designed to help you to gain familiarity with various nucleic acid structures and complexes. These exercises will be accessible through the web and should be submitted to the AI by the dates listed in the course schedule. The problem sets will be scored on a pass/fail basis. The associate instructor will not be required to grade late assignments.

Nucleic Acids Midterm Exam (10%): One two-hour exam will be given on Wednesday, November 19 from 7 to 9 PM in Room C122. Let me know as soon as possible if you anticipate a scheduling conflict.

Nucleic Acids Term Paper (15%): A 1500-word term paper is due at the beginning of the last week of classes, Monday, December 8 at 9 AM. You will be given a list of topics related to those that will be covered in class. Your paper should take the form of a short review article and should also discuss potential future directions within the field. You should present a current view of the topic; papers that fail to include references from 1996 or 1997 will be marked down.
Remember that this is an assignment for C581; papers should therefore emphasize the structure-function aspects of the topics listed. For example, an organic chemist might be more interested in a natural product than in RNA-binding proteins, but the paper should focus on the interactions of the natural product with DNA, not on the synthesis of the molecule. Similarly, a biologist writing on a transcription factor should emphasize protein-nucleic acid recognition, not transcriptional regulation.
Papers based on your lab research project, or on any work underway in your research group or rotation labs, are NOT acceptable. You may choose a topic that is not on the list, provided you clear your idea with the instructor no later than Monday, November 24. No exceptions will be made to this rule, and the instructor will not grade papers written on inappropriate topics.
Finally, please note that work that has previously been used or will be used concurrently for another class may not be submitted for C581. Any offense will be treated as an academic violation.

Nucleic Acids Final Exam (20%): A two-hour final will be given during the regularly scheduled final examination period. This exam will cover the entire nucleic acids portion of the course and will also revisit important biophysical concepts from the proteins half of the course.


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Last updated: 01/23/2001