2111: CD22 Binder Design: Round 1
|Name:||2111: CD22 Binder Design: Round 1|
|Expired:||02/25/2022 - 23:00|
|Description:||Note: This puzzle was closed early due to an error that allowed parts of the target chain to move. This puzzle has been reposted as Puzzle 2111b.
Design a protein that can bind to CD22! This puzzle enables AlphaFold predictions for your designed binder. Once you've designed a binder for the target, upload your solution for AlphaFold using the AlphaFold prediction tool. AlphaFold will predict the structure of your binder chain only (i.e. in the unbound state, in the absence of the target). If you load this prediction, then Foldit will attempt to align the prediction with your solution (i.e. in the bound state, making an interface with the target). If you continue working off of the AlphaFold prediction, you may need to make adjustments at the interface where the binder interacts with the target.
CD22 is a receptor protein found on the surface of human B cells. In some kinds of blood cancer, these B cells become malignant and proliferate throughout the body, making them difficult to treat with targeted therapy. CD22 is a helpful marker that distinguishes these B cells from other types of tissue in the body. A binder for CD22 could be useful as a kind of homing device for chemotherapy, specifically targeting the cancerous cells and leaving healthy cells unaffected by toxic chemotherapy drugs.
In this puzzle, we've presented a section of the CD22 target that we think is an appropriate binding site. The backbone and most of the sidechains are frozen, except at the binding site, where flexible sidechains are shown in color. Players should design a new protein that can tightly bind to these sidechains and recognize CD22. In order to bind the CD22 target, 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! Note that the frozen target already contains one BUNS atom at residue 7; the BUNS Objective will penalize this atom, but players may not be able to satisfy the atom with a binder and should ignore it. See the puzzle comments for Objective details.
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