Student Projects for UMass Chemistry 423 Spring 2012

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Spring 2012 Chem423 Team Projects: Understanding the chemical basis of disease and life processes


Project Instructions

1. Topics due Friday 2/24 before class

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 noon Feb 16.
Once you know your team assignment, select an available topic (not already chosen by another team); see our course website for suggestions and guidelines to 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. If you want to choose a topic not on the list, be sure that it does not already have a detailed Proteopedia page and email Prof Thompson to get approval: send the pdb code for the complex and briefly explain the disease connection or why it is interesting. Add your topic to the team list at Sandbox423 by 2/24.

2. Sandbox page displaying initial structure, description, and one green scene due by end of class workshop 2/27

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.

3. Sandbox page with each section displaying an outline and at one least green scene due by beginning of class 3/5

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 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 near-final draft, due 1 week before presentation. Presentation dates will be assigned when topics are chosen. Prof Thompson will provide suggestions for improvements to your draft; you may also request feedback earlier.

Your proteopedia page should be organized into the following required sections, with each team member responsible for one of sections a-d 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: the written description should not extend beyond the jmol window. 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. 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 with an interesting short caption describing 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? 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. 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!).

4. In-class presentations on assigned dates.


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

Aspartate receptor ligand binding domain (1wat)

Drag the structure with the mouse to rotate

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.[1] 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[2] 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 .


  1. Yeh JI, Biemann HP, Pandit J, Koshland DE, Kim SH. The three-dimensional structure of the ligand-binding domain of a wild-type bacterial chemotaxis receptor. Structural comparison to the cross-linked mutant forms and conformational changes upon ligand binding. J Biol Chem. 1993 May 5;268(13):9787-92. PMID:8486661
  2. Milburn MV, Prive GG, Milligan DL, Scott WG, Yeh J, Jancarik J, Koshland DE Jr, Kim SH. Three-dimensional structures of the ligand-binding domain of the bacterial aspartate receptor with and without a ligand. Science. 1991 Nov 29;254(5036):1342-7. PMID:1660187

Help 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.
  • 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.

Spring 2012 Chem423 Team Projects

Following any team's entry, add your nominations of the best scenes for display at the ISB Molecular playground, using the following format:

"Your Name" nominates the scene "name of green scene" with the caption "your caption".

Choose a visually attractive scene and come up with a new caption of ≤ 12 words that is interesting/understandable to a general audience. See my example under the first project. Be creative!

3. Ryan Deeney, Jeffrey Boerth, Kate Liedell, Rebecca Bishop - Diabetes 3loh (insulin receptor) Presentation 3/28/12 Draft due 3/21

Prof Thompson nominates the scene "biological dimer" with the caption "Insulin receptor signaling goes awry in diabetes".

Rebecca Bishop nominates the scene "biological dimer" with the caption "Understanding insulin receptor signaling may be the key to treating Type II Diabetes."

Stephanie Bristol nominates the scene "hexamer form" with the caption "The hexamer form of insulin that aids in storage in the pancreas but does not activate the insulin receptor."

6. Greg Keohane, Nicole Hofstetter, Gina Lein, Louis Pires, - cisplatin, 1a84 Presentation 4/9/12 Draft due 4/2

Jeffrey Boerth nominates the scene "binding interactions" with the caption "Cisplatin binding to adjacent guanine bases halts tumor cell growth in cancer therapy."

Louis Pires nominates the scene "DNA" with the caption "Cisplatin binding bends DNA creating a new direction in cancer research."

Gina Lein nominates the scene “DNA” with the caption “HMG-Protein kinks DNA further leading to tumor cell death.“

"Nicole Bundy" nominates the scene "A-DNA conformation due to Cisplatin" with the caption "Cisplatin is leaps and "bends" above the rest; bending DNA strands to fight cancer!".

Chris Carr nominates the scene "DNA" with the caption "HMG-Protein: binding and disrupting cancer cell DNA".

4. Julia Tomaszewski, Sam Kmail, Nicole Bundy, Jesse Guillet - [Student Projects for UMass Chemistry 423 Spring 2012-3|restriction enzyme/DNA complex, 1rva ]] Presentation 4/11/12 Draft due 4/4

Felix Alfonso nominates the scene "specific" with the caption "Target site recognition along the DNA Minor Groove by EcoRV endonuclease restriction enzyme"

Emily Brackett nominates the scene "recognition sequence" with the caption "EcoRV endonuclease bound to DNA to cleave between the A and T base pairs".

5. Alec Gramann, William Frantz, Felix Alfonso, Paula Preap - Bone Formation & Apoptosis & 1m4u Presentation 4/23/12 Draft due 4/16

Max Nowak nominates the scene "dimer" with the caption "Noggin-BMP-7 complex shows inhibition of chrondogenesis in chicks"

9. Di Lin, Jill Moore, Austin Virtue, Alexander Way - Caspase 3, 1RHK Presentation 4/23/12 Draft due 4/16

Julia Tomaszeski nominates the scene "DEVD-aldehyde binding" with the caption "My name is Bond - Hydrogen Bond."

Austin Virtue nominates the scene "heterotetramer" with the caption "Alpha helixes surrounded twelve stranded beta sheet structure is unique to caspases"

1. Jessica Royal, Anh Huynh, Stephanie Bristol, Emily Brackett - Catechol-O-methyltransferase, 2ZVJ, Parkinson's disease Presentation 4/25/12 Draft due 4/18

Di Lin nominates the scene "aromatic ring" with the caption "These two aromatic rings were shown to be inhibitors in vitro and vivo of catechol-O-methyltnansfenase"

Greg Keohane nominates scene "aromatic ring" with the caption "shown to be inhibitors in vitro and in vivo of catechol-O-methyltnansfenase"

Nicole Hofstetter nominates scence "here" with caption "Multitasking enzyme Catechol-O-Methyltransferase , can extraordinarily be membrane bound or water soluble, a magnificent feature of its mixed polar and non-polar groups."

Kyle Reed nominates the scene "here" (In Overall Structure) with the caption "Catechol-O-Methyltransferase and the polarity of its residues (purple=polar, gray=nonpolar)"

8. Max Nowak, Kyle Reed, Kevin Dillon, Chris Carr - dementia 1JVQ Presentation 4/25/12 Draft due 4/18

Nick Vecchiarello nominates scene "heterodimer" with the caption "heterodimer: Linkage of the L and I Chains"

2. William Yarr, Ryan Colombo, Joey Nguyen, Jacqueline Pasek-Allen - Hemoglobin 1qxd Presentation 4/27/12 Draft due 4/20

William Frantz nominates the scene "α and β Subunits" with the caption "Four subunits intertwine and align to bind O2"

Ryan Deeney nominates the scene "2Hbs Val6 interaction with hydrophobic patch" with the caption "Mutation in one amino acid causes a hydrophobic interaction, forming sickle cell hemoglobin"

Jeffrey Salemi nominates the scene "Glu6 residue of Hb" with the caption "Sickle cell anemia stems from a single mutation in Glu6".

Alec Gramann nominates the scene "αβ Dimers" with the caption "Sickle-cell anemia nickel and dimed the αβ Dimer, limiting oxygen binding."

7. Polina Berdnikova, James Hamblin, Jill Carlson, Brett Clinton - phosphatase inhibitor complexes-1nny Presentation 4/27/12 Draft due 4/20

James Hamblin nominates the scene "three different stages" with the caption "Drug design: creating a ligand for increased insulin response"

Tom Foley also nominates the scene "three different stages" with the verbose caption "This product of rational drug design blocks the active site and selectively binds localized non-active sites."

Brett Clinton nominates the scene "three different stages" with the caption "A linked fragment inhibitor to treat diabetes."

10. Adam Ramey, Jeffrey Salemi, Nicholas Vecchiarello, Tom Foley - leadzyme, 1nuv Presentation 4/30/12 Draft due 4/23

William Yarr nominates the scene "here" with the caption "Leadzyme is an enzymatic, double-stranded RNA complex called a ribozyme."

Kate Liedell nominates the scene "leadzyme" with the caption "Leadzyme: RNA can do more than information transfer in this RNA cutting ribozyme"

Questions & Answers

Here is a place to post questions and answers for each other about how to do things in Proteopedia. Here are some from me and previous students.

  • For step-by-step instructions on creating example scenes, try Proteopedia:DIY:Scenes.
  • Safari currently not working for making a scene... LKT 2/27 But it just worked for Xuni! Test saving a simple scene first.
  • A very useful color scheme is "chain" which colors separate proteins or DNA strands in different colors (first select all protein or DNA).
  • To show the biological unit, follow directions at Biological Unit: Showing. The pdb file will display the "asymmetric unit" = the smallest unit that can be replicated to generate the full crystal. Example: the protein may function as a dimer (you need biochemical experiments to tell you this -- crystallography and NMR won't tell you), but the pdb file may display a monomer (if the dimer is symmetric) or two dimers (if they have slightly different conformations in the crystals -- perhaps due to crystal contacts or perhaps representing 2 functional states of the protein!).
  • Anyone know what format we should be putting our references in?

Complete instructions for references are at Help:Editing#Citing_Literature_References.You can 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). [1] You also need to add the section:


  1. Yeh JI, Biemann HP, Pandit J, Koshland DE, Kim SH. The three-dimensional structure of the ligand-binding domain of a wild-type bacterial chemotaxis receptor. Structural comparison to the cross-linked mutant forms and conformational changes upon ligand binding. J Biol Chem. 1993 May 5;268(13):9787-92. PMID:8486661
  • 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.

  • If you suddenly can't get to your sandbox page (error message XML error: Mismatched tag at line 1), try Help:Errors

Tips from feedback/edits of your Proteopedia Projects

Please read the feedback on all of the sections to give you ideas for improving your own section -- leave the red text until you're all done with all sections.

Each section should start with the line that inserts the Jmol window: then each scene for that section will appear in that window, along side your text (which should only extend 1-2 lines beyond the jmol window).

Every jmol window should have a caption so we know what we are looking at (include the name of the molecule and pdb code) Replace "insert caption here' with 'your caption'.

Captions in each section: come up with a cool (short) caption that fits your best scene that you think would be good for the Molecular Playground -- something that's understandable on its own and will capture the attention of a broad audience.

Careful with repetition of the same points in multiple sections -- instead organize the topics logically and you can have multiple people contribute to a section if you want.

Feel free to work together on sections and add people to the credits if that helps to make a coherent and organized story.

Follow the correct format for references, including citations in text -- see instructions and link above.

Make green scenes to illustrate your points, and weave your scenes into the text.

Use colored text to help the reader easily see your points in the scene and to keep your text concise. For example "This view shows the 2 alpha helices packed against the 4-stranded antiparallel beta sheet." The word view would like to a scene in which the alpha helices are red and the beta sheet is blue. Go into edit mode on this page to copy the colored text section for use on your page.

Avoid a list of miscellaneous facts. Choose the most interesting points to tell us in some detail and illustrate with green scenes.

Keep the length of your text similar to the length of the jmol window.

Proteopedia Page Contributors and Editors (what is this?)

Lynmarie K Thompson

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