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835: SOD1 Hotspot
Status: Closed


Name: 835: SOD1 Hotspot
Status: Closed
Created: 01/17/2014
Points: 100
Expired: 01/27/2014 - 20:00
Difficulty: Intermediate
Description: Mutations in the gene encoding the SOD1 protein cause a subset of cases of amyotrophic lateral sclerosis, or Lou Gehrig's disease. There is some evidence that the two SOD1 subunits in the dimer separate as part of the aggregation process, so a molecule that is able to "glue" the dimer together could help to slow or halt the molecular events that lead to the disease. As a starting point for designing such a "glue", we'd like you to find good places at the interface between the SOD1 subunits to place a small, three-residue fragment. In designing the sequence of this fragment, keep in mind that hydrophobic interactions (interactions with orange residues) are much more likely to give high affinity and specificity than polar interactions (interactions with blue residues), so we recommend focusing on placing hydrophobic side-chains in the cleft between the subunits. Good luck!
Categories: Design, Overall

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v_mulligan's picture
User offline. Last seen 3 years 13 weeks ago. Offline
Joined: 03/04/2009
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SOD1 and metals

One player pointed out that SOD1 is a metalloprotein (i.e. it has metal atoms as part of its structure -- one copper and one zinc per subunit). This is true, though they're not shown in this puzzle. I stripped out the metals for this puzzle because they're far from the region where we want our peptide to bind (the dimer interface), and because the puzzle would have required a little bit of extra setup on our part in order to make sure that Foldit didn't choke on the metals. The bottom line is that I was being a little bit lazy by leaving them out, but they wouldn't make a difference in this case!

brow42's picture
User offline. Last seen 1 year 36 weeks ago. Offline
Joined: 09/19/2011
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How strongly do you want us to leave the terminals pointing out, and not buried?

bkoep's picture
User offline. Last seen 8 hours 32 min ago. Offline
Joined: 11/15/2012
Groups: Foldit Staff
Don't worry about it

It's okay if the terminals of your small peptide are buried or directed toward the target protein. These peptides might be hard to map directly onto a larger protein, but such high-scoring hotspots are still very informative.

v_mulligan's picture
User offline. Last seen 3 years 13 weeks ago. Offline
Joined: 03/04/2009
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Good question!

That's a good question, though. Since I will be extending the "stub", I will ultimately need exposed termini -- but bkoep is correct; you don't need to worry about it. The most important thing for this puzzle is getting the side-chains to dock well at the SOD1 dimer interface. I can tweak the backbone after the fact for subsequent design, so designs with buried termini are still perfectly fine.

Joined: 11/10/2007
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Scores Adjusted

The scores for this puzzles have been adjusted and updated. See http://fold.it/portal/node/996740 .

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