puzzle picture
2005b: IL-2R Binder Design: Round 1
Status: Closed


Name: 2005b: IL-2R Binder Design: Round 1
Status: Closed
Created: 06/12/2021
Points: 100
Expired: 06/18/2021 - 23:00
Difficulty: Intermediate
Description: Note: This puzzle replaces the original Puzzle 2005 which used a mis-calibrated score function. Players may load in solutions from the original Puzzle 2005.

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.
Categories: Design, Overall

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Joined: 11/15/2012
Groups: Foldit Staff

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.

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Developed by: UW Center for Game Science, UW Institute for Protein Design, Northeastern University, Vanderbilt University Meiler Lab, UC Davis
Supported by: DARPA, NSF, NIH, HHMI, Amazon, Microsoft, Adobe, Boehringer Ingelheim, RosettaCommons