1982: Tie2 Binder Design: Round 2
|Name:||1982: Tie2 Binder Design: Round 2|
|Expired:||04/23/2021 - 23:00|
|Description:||Design a protein to bind to the Tie2 receptor! This puzzle is much like the Round 1 puzzle, except that we've increased the threshold for the Contact Surface Objective. Aim for a Contact Surface value of at least 500!
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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