Closed since over 6 years ago
Intermediate Overall DesignDesign a protein that binds IL-7R!
Interleukin 7 receptor (IL-7R) is a protein that helps regulate the human immune system, and is an important target in cancer therapy research. In this puzzle, players start with two frozen helices bound to the IL-7R target (also frozen). Players can fold and design about 20 residues flanking the binding helices, with the goal of creating a well-folded protein that can bind the IL-7R target! Players may also redesign residues on the backside of the binding helices, but residues at the IL-7R interface are frozen in place. The most promising designs will have lots of helical and/or sheet structure with only short loops, and will have a well-packed, buried core. There are several Objectives in place; see the puzzle comments for details.
This is the seventh ninth puzzle in the IL-7R binder series, meant to generate a large diversity of designs that can be tested in a high-throughput binding experiment! Due to time constraints, puzzles in this series will be online for only 4 days at a time. See the blog for more information. Remember, you can use the Upload for Scientists button for up to 5 designs that you want us to look at, even if they are not the best-scoring solutions!
Residue IE Score (max +500)
Monitors that all PHE, TYR, and TRP residues are scoring well.
Core Existence (max +1000)
Ensures that at least 25% of residues are buried in the protein core.
SS Design (max +200)
Penalizes all CYS residues. Penalizes GLY, ALA, SER, THR in helices. Penalizes GLY, ALA in sheets.
Residue Count (max +100)
Penalizes extra residues inserted beyond 110, at a cost of 20 points per residue. Players may use up to 115 residues in total.
i'v got +250 instead of +200
Hmm, that shouldn't be possible… Can you share your solution with scientists? Could be a bug.
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"This is the seventh puzzle in the IL-7R binder series"
Really !! Are you sure ??
Glad to see some close reading of the puzzle descriptions ;)
I've shared this solution. It is very unstable - any wiggle drops +250 bonus down to normal value
As noted by JSmith48 in global chat, segments 46-51 can move.
If you draw 3 bands from these segments to a point in space, and change the strength of each band to 10, wiggle will move the section a long way. The other snippets of IL-7R can't be moved this way.
When you disable or delete the bands, there is some tendency for 46-51 to migrate back closer to where it started. It never shows any red constraint lines, however, even with "show constraints" checked in view options.
I checked the previous four rounds of this series. Segments 46-51 don't move in these puzzles.
That was an oversight on our part; segments 46-51 are supposed to be fixed in place! I don't expect this to have a huge effect on the puzzle results, but we'll have to take a close look at the solutions after the puzzle closes.
lots of us found ourselves locked out due to server shut down. If you need a revisit let us know, though Fiendish has a stunning fold for this
