Student Projects for UMass Chemistry 423 Spring 2012

Spring 2012 Chem423 Team Projects: Protein-ligand Complexes for Understanding Drug and Disease Mechanisms

Project InstructionsProject Instructions

1. Topics and 1 green scene: Sandbox pages displaying initial structure and one green scene due at class workshop 2/27/12

Teams of 4 people will be assigned, to include both chemistry and chemical engineering majors on most teams. You may request one teammate by emailing the TA by Feb 17.

Select an available topic (not already chosen by another team) from the list or find a simple protein-ligand complex (eg protein-drug, nucleic acid-drug, or protein-DNA) with a known structure in the pdb that interests your team. For any topic not on the list, email Prof Thompson to get approval: send the pdb code for the complex and briefly explain the disease connection or why it is interesting.

Start your assigned sandbox page: Find the pdb id for your protein-ligand complex in the Protein Data Bank. 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.

2. Project near-final draft, due 1 week before presentation. Prof Thompson will provide suggestions for improvements (you may also request feedback earlier, if you have all sections started and containing one green scene. Your proteopedia page should be organized into the following 4 required sections, with each team member responsible for one of these sections of the team project. Each section should have its own jmol window. Provide an interesting and nontechnical description in words, and illustrate points about the complex with green scenes. Be concise: the written description should not extend beyond the jmol window. a. Introduction

Introduce the protein function and the disease treated by the drug. This must be written in your own words with citations to your sources.You cannot include a copyrighted figure unless you request permission to use it.

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? Below I illustrate the start of an "overall structure" section on GFP. 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. Drug binding site

Describe features of the drug 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 protein. 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).

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

Introduction -- name of team member

Overall structure -- name of team member

Drug binding site -- name of team member

Additional features -- name of team member

f. 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!).

3. In-class presentations, to be announced

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 Aspartate receptor ligand binding domain (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

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

Project Teams, Topics, Links, and Presentation DatesProject Teams, Topics, Links, and Presentation Dates

C See comment on your page.

Example (but not a drug complex): Lynmarie Thompson, ..., ..., ... - Asp receptor in complex with Asp (above)

Monday 4/25/11

Nick DeGraan-Weber, Jackie Dorhout, Rachael Jayne, Mike Reardon - flu neuraminidase in complex with tamiflu

John Hickey, Josh Drolet, Josephine Harrington, Andrea Simoni - influenza M2 proton channel

UMass Chem 423 Student Projects 2011-1:

Wednesday 4/27/11

Brittany Forkus, Katie Geldart, Elizabeth Schutsky, Breanna Zerfas - Beta Adrenergic GPCR

Lucia Tringali, Shaina Boyle, Jaclyn Somadelis , Dany Mbakop -- HIV Protease

Andy Kim, Zach Brentzel, Tyler Vlass, Zach Hitzig -- Acetylcholinesterase

Friday 4/29/11

Varun Chalupadi, Anthony Laviola, Tiffany Brucker, Alan Stebbins - Cyclooxygenase

UMass Chem 423 Student Projects 2011-2:

Inna Brockman, Robert Nathan, Sarena Horava, Nick Cadirov - p38 kinase

David Peltier, Donald Einck, Ethan Leighton, Chris Coakley - Rituximab Fab

Monday 5/2/11

Max Moulton, Sally Stras, Jordan Schleeweis, Anh Huynh -- HIV reverse transcription

Chris Brueckner, Daniel Roy, John Clarkson, Justin Srodulski -- Ketamine in binding complex with NMDA receptor

Lyes Khendek, Paul Breslin, William Rowley, Joe Perito, Ashley Rivera - G-Quadruplex

Students looking for group membersStudents looking for group members

Each group should contain at least one person from a different primary major (typically Chemistry or Chemical Engineering) than the rest.

List yourself + your major, list partial groups looking for members, list your complex if you have chosen one. Contact others to form a group.

4/1/11 update by Prof Thompson: The remaining students can go ahead and form teams regardless of major.

Luis Cristian, Chem major, lcristia@student.umass.edu - looking to be in a group with chem eng

Help EditingHelp Editing

Hint: Ctl-click or right-click on links below and select "Open Link in New Window"

Start with Help in the navigation box on the left. Some things I've found useful:

• Follow the step-by-step written Primer.

• For step-by-step instructions on creating example scenes, try Proteopedia:DIY:Scenes.

• For editing help, try Help:Editing. Guidelines for avoiding plagiarism are listed here: Proteopedia:Guidelines for Ethical Writing.

• You can use the edit button on any page to find out how other users created effects that you see in the text (not the scenes).

[Wikimedia cheat sheet]

[General help with Wiki editing], plus more [Wiki Text examples]

Some of the above are for help editing Wikipedia pages, but the syntax is mostly the same. Proteopedia ADDS protein stuff to the WikiMedia markup language, which powers both WEB sites.

Questions & AnswersQuestions & Answers

Here is a place to post questions and answers for each other about how to do things in Proteopedia:

A very useful color scheme is "chain" which colors separate proteins or DNA strands in different colors (first select all protein or DNA).

Anyone know what format we should be putting our references in?

For references, follow the format used in the example on the Asp receptor and they will be put in automatically. You just find out the PMID code (listed in pubmed for example) and insert it into the following, at the place where you want the reference cited (click edit to see what is actually inserted here). You also need to add the section:

References

Hey guys this is just a useful tip: If you get an xml error after you try to save your changes it is due to the green scene coding. Our group experienced this issue and it would not let us access our sandbox. In order to fix this go back (or find the page to edit in your history) and delete the green scene code that was just entered. Then save the page and you should be back to your sandbox. This may be trivial to many, but just throwing it out there.

To highlight some interesting portion of your protein: Under the selections tab, you can "limit to residue numbers." So for example enter in 60-65, then click "replace selection" below. Then if you go to the colors tab you can pick a color for just the residues you have selected. If it is a loop or if they are hard to see you can go to the representation tab and set selection to ball and stick or spacefill.

It is also useful to click the "selection halos:" box under the picture. That shows you what you have in your selection.