Foldit

2064: CD47 Binder Design: Round 4

Closed since over 4 years ago

Summary

Created: October 28, 2021
Expires: November 05, 2021 at 23:00 UTC
Max points: 100

Description

Design a protein that can bind to CD47! 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.

CD47 is a protein displayed on surface of human cells. Normally, CD47 is presented to the immune system as a "friendly" signal, and can prevent an over-zealous immune system from attacking healthy human tissue. However, some types of cancer will over-produce CD47 as a way to evade the immune system, camouflaging a tumor as "friendly" human tissue. A protein that binds to CD47 might be useful for treating these types of cancer. We'd like to design a protein binder that can block CD47 recognition by the immune system, and allow immune cells to attack tumors in the body.

In this puzzle, we've presented a section of the CD47 target that is recognized by the immune system. 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 CD47 recognition. In order to bind the 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! See the puzzle comments for Objective details.