| 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 | |
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:
| 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% |
| 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. |
| 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 |
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
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.