1108: Compact 37-Residue Marburg Virus Inhibitor Design
|Name:||1108: Compact 37-Residue Marburg Virus Inhibitor Design|
|Expired:||07/08/2015 - 23:00|
|Description:||Based on the results from Puzzle 1073: Marburg Binder Design with Disulfides (see the feedback on the Foldit blog for an idea of what we're looking for), we'd like to revisit this design target. The Marburg virus is a cousin of the Ebola virus, and causes a similarly deadly hemorrhagic fever. The largest outbreak, in 2004, had a 90% mortality rate. Understandably, we'd like an anti-viral agent to treat this disease. Like Ebola, Marburg virus uses a viral surface glycoprotein to grab onto certain human cell membrane proteins and enter human cells. It is our hope that, by blocking the binding site on this glycoprotein that recognizes and binds to human cellular proteins, we can prevent cellular entry and neutralize the virus. To this end, we want you to design a small (37-residue), heavily disulfide cross-linked peptide that can bind to the Marburg glycoprotein. As a starting point, we're giving you a loop taken from a neutarlizing antibody. This puzzle is similar to Puzzle 1073 in that you will get a substantial bonus for forming up to two disulfides. However, we have added the following: -- A core existence filter. You'll get a substantial bonus for making a hydrophobic core. (We want compact, nicely-folded peptides, not elongated designs. Please see the Foldit blog for feedback from the last Marburg puzzle, with examples of the sorts of designs that we'd like to see.) -- A fragment quality filter that penalizes portions of your design that are in unusual conformations that do not resemble those of natural proteins. (Note that this unfortunately scores the entire structure, so all players will see a penalty of 1400 points for parts of the Marburg glycoprotein and for the antibody loop. Because this penalty is the same across the board, it gives no player an advantage or a disadvantage over any other player. Additional penalties can result from having bad loops in the design, though.) -- A larger penalty for glycine. While glycine is sometimes necessary, too many promote disordered peptides. -- A larger bonus for proline. Prolines are terrific for making a peptide nice and rigid. The filters can be a bit slow, so you might want to disable them during design and only re-enable them as needed.|
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