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971: Ebola glycoprotein peptide inhibitor design (REPOSTED as 971c)

Closed since over 11 years ago

Intermediate

Summary

Created
August 19, 2014
Expires
Max points
100
Description

We would like you to design a small (25-residue) peptide that can bind to and block the Ebola glycoprotein. The glycoprotein is a viral surface protein that allows the Ebola virus to enter human cells. A small peptide inhibitor of this protein would therefore represent a candidate therapeutic for treating this deadly disease. We are starting you with a hotspot "stub" that was the top-scoring result from the earlier stub-finding puzzle, number 846. (Congratulations to AnthropicDreams!) We have extended this stub with twenty-two additional residues that you can design.

A small peptide in this size range probably won't fold the way a protein would. Some considerations -- good hydrophobic packing, lack of holes in the core, good hydrogen bonding, presence of secondary structure, etc. -- will be the same, but in addition, heavy disulfide cross-linking is often necessary for stability in this size range. You will get a considerable bonus for forming up to three disulfide bonds (for a total of five, counting the two disulfide bonds already present in the Ebola target protein). Many natural plant and animal toxins are small peptides, and it is common to see three disulfide bonds in a "leapfrog" pattern (i.e. cys1-cys4, cys2-cys5, cys3-cys6) for maximal stability. The starting point for this puzzle has three disulfides in this "leapfrog" pattern, but this might not be the optimal disulfide placement or backbone topology. Feel free to change the secondary structure, move the disulfides around, or otherwise improve on this!

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Comments

wisky Lv 1

When trying to idealize SS on this puzzle, I get a pop saying "Setup not TYPE_CARTESIAN." This has probably already been noted.

v_mulligan Lv 1

That is definitely odd – that particular error shouldn't be coming up in that situation. I have been able to reproduce it, though, and will talk to the devs about it at our weekly meeting.