Closed since over 6 years ago
Intermediate Overall DesignNote: This puzzle was mistakenly set to close on August 19. The puzzle close date has been reset to August 17, at 23:00, to keep the number of open puzzles at a reasonable level.
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 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 fifth 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!
100 pts.
11,597
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 +275)
Penalizes extra residues inserted beyond 110, at a cost of 55 points per residue. Players may use up to 115 residues in total.
maybe 55 points for extra residues is a bit excessive. would like to try something longer and more elegant especially on the transition from the 81-99 helix
That penalty was calibrated from monomer design puzzles; it might make sense to ease up on the penalty for these IL-7R Binder puzzles.
The next Round 6 puzzle will continue to use the 55 point penalty, but we'll do some analysis and maybe make some adjustments in future rounds.
