Student Projects for UMass Chemistry 423 Spring 2015

Understanding the chemical basis of disease and life processesUnderstanding the chemical basis of disease and life processes

See Sandbox423 for Teams, Topics, and links to projects

1. Optional Teammate requests: You may request one teammate by 2/2 in Moodle.

Teams of 6 people will be assigned, to include both chemistry and chemical engineering majors on most teams.

2. Topic and pdb code due in Moodle Monday 2/9 11pm

Once you know your team assignment, select an available topic Must be unique: first-come, first-served, so check the posted list in Moodle to be sure that your topic has not already been chosen. Follow the guidelines for topics (see Moodle). Choose from the list of suggested topics, OR choose another topic of interest and check (1) to be sure it is not on the "Topics to avoid" list, and (2) check with the instructor. All topics (suggested or otherwise) must be checked to be sure there is not already a detailed Proteopedia page for the same complex or same pdb code.

3. Sandbox page for your team started and "See Also" section completed by Wednesday 2/25.

Edit one of the 10 entries at Sandbox423 by entering your team's names, topic and pdb code. Go to your assigned sandbox and edit to complete the "See Also" section: add links to any related Proteopedia Topic Pages (not pages titled with the pdb code). Search for these, for example at http://proteopedia.org/wiki/index.php/Category:Topic_Page, Topic_pages, and Proteopedia:structure_Index. If you find another useful search strategy, post it under Help at Sandbox 423. If there is another page describing a complex with the same or a very similar molecule, you will need to choose a new topic.

2. Sandbox page displaying initial structure and one green scene due by end of class workshop 2/27 -- bring your computers to class

In your assigned sandbox page click "edit this page" (top) and follow the directions to insert your rotating structure on your page. Describe and illustrate with a green scene the secondary structure of your protein.

3. Sandbox page with each section displaying an outline and at one least green scene due by beginning of class 3/11 -- bring your computers to class

Each team member should read the primary reference for the pdb structure and create an outline for their section and at least one green scene. Teams will meet briefly during class to discuss the overall organization as needed to make it logical and avoid duplication. As individuals proceed to create their sections, they should watch the other sections and stay in contact as needed to create a coherent overall project.

4. Project completed (all sections) by Fri 4/3.

Your proteopedia page should be organized into the following required sections, with each team member responsible for one of sections a-f of the team project. Each section should have its own JMol window. Provide an interesting description (suitable for non-experts), and illustrate your points about the complex with multiple green scenes. Be concise (<300 words)! Do not include any copyrighted figures! All sections must be written in your own words with citations to your sources, following the reference format in the example below (go into edit this page, to see how these references were done). You may include links to other interesting information or scenes but you must create your own scenes for display on your page.

Make it interesting and accessible to a non-scientist! Show clearly some chemical details to illustrate the chemistry of life processes!

a. Introduction

Introduce the protein function, how it is related to a disease, and what is important about the ligand in the complex. Make a green scene suitable for the Molecular Playground: an attractive and informative illustration of the protein complex. . Include a clever caption for potential display at the Molecular Playground -- this caption must be short, ideally < 10 words.

b. Overall structure

Describe the overall structure of your protein in words and make "green scenes" to illustrate your points. What elements of secondary structure are present (ie 5 alpha helices and 2 beta strands) and how are they organized? Additional description and green scenes could illustrate the polar/nonpolar distrubution of amino acids (is the inside of the barrel polar or nonpolar?), packing of amphipathic elements, etc.

c. Binding interactions

Describe features of the drug or ligand or protein-protein binding site in words and make "green scenes" to illustrate your points. Show the interactions that stabilize binding of this molecule to the protein (ie H bonds).

d. Additional features

Describe and use green scenes to illustrate additional features of the macromolecule. What you do here depends on what information is available. If a structure of the protein-substrate complex is available, you could compare protein interactions with the substrate vs. with the drug. If the drug is a transition state inhibitor, explain and illustrate that (eg include a reaction scheme with structures of the substrate, transition state and product -- but don't borrow a published scheme).

e. Quiz question 1

Pose an interesting, quiz-worthy question that involves thinking and investigating the molecule with the green scenes that you provide here.

f. Quiz question 2

Pose an interesting, quiz-worthy question that involves thinking and investigating the molecule with the green scenes that you provide here.

g. See also

For the 2/25 deadline, all team members should look for related Proteopedia pages (e.g. same protein but with different ligands) and post links here.

h. Credits -- at the end list who did which portion of the project:

Introduction -- name of team member

Overall structure -- name of team member

Binding interactions-- name of team member

Additional features -- name of team member

Quiz question 1 -- name of team member

Quiz question 2 -- name of team member

Teams with 7 members can have 2 people work on the Binding interactions or Additional features section.

i. References

This will include the published paper that describes your structure (the reference associated with your pdb code). You will get much of your information about specific interactions to look for and highlight in the structure from this reference (which is much easier than trying to find these on your own with no guidance!).

ExampleExample

This is a complex between a macromolecule and its ligand (but this ligand is not a drug) that illlustrates the use of green scenes:

spinqualitylabelsall models Bacteria use this protein to "smell" their environment, 1wat Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Asp Receptor Ligand-binding domain

Overall structure

The ligand binding domain of the aspartate receptor () ) is a dimer of two 4-helix bundles that is shown here with the bound. In this the N and C termini are at the bottom of the structure; this is where the connections to the transmembrane helices have been truncated.

Ligand binding site

When the protein is colored according to , residues at the ligand site are the most conserved. Interactions that stabilize ligand binding include hydrogen bonding from Tyr149 and Gln152 backbone carbonyls and Thr154 sidechain OH to the and hydrogen bonding from the sidechain nitrogens of Arg64, Arg69, and Arg73 to the two .

References