Closed since over 6 years ago
IntermediateNote: This puzzle was closed early, due to an error in the puzzle setup that allowed free movement of the IL-7R binding helices. The puzzle has been reposted as Puzzle 1723b.
Design 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 between 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 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 tenth 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! The binding helices in this puzzle are the same as in Round 9, but with with the designable region between the helices instead of at their termini. 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 +250)
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.
In the prior versions the helices were fixed, in this one a wiggle all allowed them to move away from the binding site.
Thanks for the quick feedback, I'm sorry we didn't see it earlier! We'll have to pull the puzzle and repost it.
