Placeholder image of a protein
Icon representing a puzzle

2026: IL-2R Binder Design: Round 3

Closed since over 4 years ago

Intermediate Overall Design

Summary

Created
July 30, 2021
Expires
Max points
100
Description

Design a protein that can bind to the IL-2 receptor (IL-2R)! IL-2 is a signaling protein that helps to regulate the human immune system. When it binds to the IL-2 receptor on the surface of an immune cell, it can induce the immune cell to change its behavior or differentiate into a new cell type. The precise effects of IL-2 vary widely for different cells, depending on the cell type, the local environment, and even the concentration of IL-2. A synthetic form of IL-2 is approved in the U.S. to treat certain types of cancer, but is associated with severe side effects. We'd like to design a protein binder that can block binding at the IL-2 receptor and attenuate IL-2 signaling.



In this puzzle, we've presented a section of the target receptor that normally binds IL-2. The backbone and most of the sidechains are frozen, except at the binding site, where flexible sidechains are shown in color. Players can design a new protein that can bind to these sidechains and block IL-2. In order to bind the target receptor, designs will need to make lots of hydrophobic contacts and satisfy any polar atoms that are buried at the interface. But designs will also need to have lots of secondary structure (helices or sheets) and a large core, so that they fold up correctly! See the puzzle comments for Objective details.

Top groups

  1. Avatar for Anthropic Dreams
    1. Anthropic Dreams
    100 pts. 13,833
  2. Avatar for Go Science 2. Go Science 68 pts. 13,785
  3. Avatar for Contenders 3. Contenders 44 pts. 13,592
  4. Avatar for Void Crushers 4. Void Crushers 27 pts. 13,433
  5. Avatar for Marvin's bunch 5. Marvin's bunch 16 pts. 13,303
  6. Avatar for Beta Folders 6. Beta Folders 9 pts. 13,256
  7. Avatar for Gargleblasters 7. Gargleblasters 5 pts. 13,149
  8. Avatar for BOINC@Poland 8. BOINC@Poland 3 pts. 13,050
  9. Avatar for Australia 9. Australia 1 pt. 12,813
  10. Avatar for L'Alliance Francophone 10. L'Alliance Francophone 1 pt. 11,209
  1. Avatar for BootsMcGraw 31. BootsMcGraw Lv 1 19 pts. 12,797
  2. Avatar for Maerlyn138 32. Maerlyn138 Lv 1 18 pts. 12,666
  3. Avatar for toshiue 33. toshiue Lv 1 17 pts. 12,649
  4. Avatar for jausmh 34. jausmh Lv 1 16 pts. 12,639
  5. Avatar for johnmitch 35. johnmitch Lv 1 15 pts. 12,560
  6. Avatar for fiendish_ghoul 36. fiendish_ghoul Lv 1 14 pts. 12,515
  7. Avatar for phi16 37. phi16 Lv 1 13 pts. 12,418
  8. Avatar for georg137 38. georg137 Lv 1 12 pts. 12,376
  9. Avatar for ZeroLeak7 39. ZeroLeak7 Lv 1 11 pts. 12,375
  10. Avatar for nspc 40. nspc Lv 1 10 pts. 12,369

Comments

bkoep Staff Lv 1

DDG Metric (max +2000)
The predicted binding energy of your design. The goal DDG is -40.0 or less.

Contact Surface (max +2000)
Measures how much of your binder surface is in close contact with the target protein. The goal Contact Surface is 500 or more.

Buried Unsats (max +500)
Penalizes 100 points for each polar atom that cannot make any hydrogen bonds.

Core Existence (max +1500)
Ensures that at least 25 percent of residues are buried in the core of the monomer unit.

Interaction Energy (max +500)
Monitors that all large PHE, TYR, and TRP residues are scoring well.

Ideal Loops (max +500)
Penalizes any loop region that does not match one of the Building Blocks in the Blueprint tool. Use "Auto Structures" to see which regions of your protein count as loops.

SS Design (max +500)
Disabled use of CYS residues. Penalizes GLY, ALA residues in sheets and helices.