1814c: Coronavirus Binder Design: Round 4
|Name:||1814c: Coronavirus Binder Design: Round 4|
|Expired:||03/26/2020 - 23:00|
|Description:||Note: This puzzle replaces Puzzle 1814b, with changes that should make it easier to build Ideal Loops around the frozen binding helix. Players may load in solutions that were saved in the original Puzzle 1814 or 1814b.
Design a binder against coronavirus! This is Foldit's fourth coronavirus puzzle, which challenges players to design an antiviral protein that could bind to the 2019 virus and disrupt viral infection. This puzzle is very similar to Round 3, but we've adjusted some things to make things a little easier for players (like removing the cutpoints). The starting structure provides a helix fragment that is already known to bind to the coronavirus, and Foldit players can design a new protein that includes this fragment. Players should focus on building up a protein with a large core of orange hydrophobics, and the best designs will also make additional contacts with the target. See our latest blog post for details about how Foldit solutions will be analyzed once the puzzle closes! Solutions from previous puzzles are incompatible with this puzzle, so players may NOT load in previous work.
In late 2019, a new highly-infections virus emerged out of Wuhan, China. This virus belongs to the coronavirus family, and is similar to the virus that caused the SARS epidemic in 2002. Coronaviruses display a "spike" protein on their surface, which binds tightly to a receptor protein found on the surface of human cells. Once the coronavirus spike binds to the human receptor, the virus can infect the human cell and replicate. In recent weeks, researchers have determined the structure of the 2019 coronavirus spike protein and how it binds to human receptors. If we can design a protein that binds to this coronavirus spike protein, it could be used to block the interaction with human cells and halt infection!
In this puzzle, players are presented with the binding site of the coronavirus spike protein. The backbone and most of the sidechains are completely frozen, except for flexible sidechains at the binding site, where the spike protein normally interacts with the human receptor protein. This puzzle also includes helix fragment from the human receptor. Players can fold and design about 55 residues flanking the binding helix, with the goal of creating a well-folded protein that can bind the target in the same way as the human receptor. Final designs will need to make additional hydrophobic contacts and H-bonds with the flexible sidechains at the target binding site. 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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