puzzle picture
846: Ebola hotspot discovery
Status: Closed

Summary

Name: 846: Ebola hotspot discovery
Status: Closed
Created: 02/13/2014
Points: 100
Expired: 02/24/2014 - 23:00
Difficulty: Intermediate
Description: We would like to design a peptide to treat the Ebola virus. This puzzle is a hotspot discovery puzzle, meaning that we would like you to find a good place in which to fit a small peptide "stub" in a particular hydrophobic binding pocket on the Ebola virus glycoprotein. We will then use the best stub placements as starting points for designing a larger molecule. Blocking this pocket on the Ebola glycoprotein will prevent the glycoprotein from binding to proteins on host cells, and should thereby block viral entry into host cells. We're starting you with a tryptophan, but you can mutate the stub residues to whatever you like. Remember that you can share interesting designs with the scientists, regardless your score!
Categories: Design, Overall

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Comments

bertro's picture
User offline. Last seen 2 hours 15 min ago. Offline
Joined: 05/02/2011
Groups: Beta Folders
Is this the real Ebola virus?

Is this the real Ebola virus? I mean is it really what it looks like. Even with segment 157-158 stretched like that?

v_mulligan's picture
User offline. Last seen 16 weeks 4 days ago. Offline
Joined: 03/04/2009
Groups: None
A protein on the virus -- yes.

Yes, the large molecule in this puzzle is a real x-ray crystallographic structure of a protein found on the surface of the Ebola virus (the Ebola glycoprotein, or GP). Viruses are typically about ten to a hundred times larger than individual protein molecules. An Ebola virus looks like a little tube about a thousandth of a millimetre long and a ten-thousandth of a millimetre thick. Its surface is studded with hundreds of these GP molecules. (Here's a computer-generated picture of an Ebola virus. The little magenta things studding the outer surface are GP molecules.) And yes, some segments in the protein look a bit odd, though the actual molecule is a trimer of heterodimers, so there might be interactions with other subunits that stabilize the odd-looking bits. I stripped the protein down to the bit for which we want to design a binder in the interests of simplicity.

GP binds to proteins on the surface of human cells and triggers fusion of the viral membrane with the human cell membrane, which allows the virus to inject its genetic material into a host cell and thereby use the host cell to replicate itself. If we can block the function of GP with a peptide that plugs up its binding site, then we can hopefully prevent the Ebola virus from invading a host cell.

v_mulligan's picture
User offline. Last seen 16 weeks 4 days ago. Offline
Joined: 03/04/2009
Groups: None
Oh, I see

Ah, I just noticed segment 157-158. That's just a display artifact; those two residues aren't actually connected. Since that segment is far from the binding site, and since the backbone of the protein can't move in this puzzle, it shouldn't affect anything, but if I were to set this up again, I'd make sure that there was a proper cut between those two residues so that it looks right. Since it won't affect gameplay, I don't think it's necessary to repost the puzzle. Sorry about that -- it is kind of funny looking.

bertro's picture
User offline. Last seen 2 hours 15 min ago. Offline
Joined: 05/02/2011
Groups: Beta Folders
Thanks

for the long and short answers, very informative and appreciated.

wisky's picture
User offline. Last seen 1 week 3 days ago. Offline
Joined: 07/13/2011
Puzzle length

Why is this puzzle so long (12 days)?

Joined: 03/08/2013
Groups: None
So, it's a virus. I just

So, it's a virus. I just looked it up on Wikipedia, and (conveniently,) it has a picture of a protein of the virus.

http://upload.wikimedia.org/wikipedia/commons/thumb/f/ff/Ebola_virus_em.jpg/220px-Ebola_virus_em.jpg

If you look at it close enough, it looks a little like a drawing. Or a shoelace.

v_mulligan's picture
User offline. Last seen 16 weeks 4 days ago. Offline
Joined: 03/04/2009
Groups: None
Much larger scale

That electron micrograph image is of a much, much larger scale than what we're showing you here. It's not "a picture of a protein of the virus"; it's a picture of a whole virus. One of these viral glycoprotein molecules would be a tiny speck on the surface of the virus, lost in the black outline.

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Developed by: UW Center for Game Science, UW Institute for Protein Design, Northeastern University, Vanderbilt University Meiler Lab, UC Davis
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