2135: TGF Receptor Binder Design: Round 17
|Name:||2135: TGF Receptor Binder Design: Round 17|
|Expired:||04/22/2022 - 23:00|
|Description:||Design a protein that can bind to the TGF-beta receptor! This puzzle has a reduced BUNS penalty so that players can focus on other Objectives--but don't forget about BUNS completely! AlphaFold predictions are available 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.
TGF-beta is a human signaling molecule that cells use to communicate with one another. In some circumstances TGF-beta inhibits the immune response, and is important for regulating over-active immune cells if they risk damaging normal human tissue. However, certain types of tumors release extra TGF-beta to deceive the immune system so that the tumors can grow unchecked. We'd like to design a protein binder that can stick to the TGF-beta receptor and prevent this deceptive signaling. A successful binder could be part of a selective cancer treatment that helps the natural immune system fight tumor growth.
In this puzzle, we've presented a section of the target receptor that normally binds TGF-beta. 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 TGF-beta. 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! We know from prior experiments that this is an exceptionally difficult binding target, so the Contact Surface Objective is more stringent, and will not max out until you reach Contact Surface > 500. See the puzzle comments for Objective details.
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