1956: Influenza HA Binder Design: Round 2
|Name:||1956: Influenza HA Binder Design: Round 2|
|Expired:||02/19/2021 - 23:00|
|Description:||Design a protein to bind to influenza virus! This puzzle has a Move Limit of 250 moves; after that, you will be unable to improve your solution, but you can restart the puzzle to reset your move count. The Move Limit is meant to encourage players to try multiple solutions to the puzzle, instead of spending a lot of time optimizing a single solution.
The hemagglutinin (HA) protein is displayed on the surface of the influenza virus, where it can bind to receptors on human cells. Once the HA protein binds to a human receptor, the entire HA protein changes shape, springing open to trigger membrane fusion so that the virus can infect the human cell. We want to design a protein that can bind to the pre-fusion shape of HA, to stop it from springing open and thereby blocking infection.
In this puzzle, we've presented a section of the target HA protein in the pre-fusion shape. 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, stabilizing this pre-fusion shape. In order to bind the HA 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! Beware the large sugar sidechain next to the binding site, which has lots of polar atoms that can form unstable BUNS if you are not careful. See the puzzle comments for Objective details.
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