2129: Tie2 Binder Design: Round 5
|Name:||2129: Tie2 Binder Design: Round 5|
|Expired:||04/08/2022 - 23:00|
|Description:||Design a protein to bind to the Tie2 receptor! This puzzle has a reduced BUNS penalty so that players can focus on other Objectives--but don't forget about BUNS completely! 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.
Tie2 is a human protein that helps to regulate the maintenance and growth of blood vessels throughout the body. Normally, the Tie2 receptor binds a growth factor called angiopoietin, a signaling molecule that triggers the growth of new blood vessels. However, Tie2 overactivity has been implicated in several types of cancer, since rapidly-growing tumors require lots of new blood vessels to provide nutrients. We want to design a protein that could bind to Tie2 and block angiopoietin. A successful binder might be useful as a drug to modulate Tie2 activity that is necessary for tumor growth.
In this puzzle, we've presented a section of the target Tie2 protein that normally binds angiopoietin. 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 angiopoietin. In order to bind the Tie2 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.
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