Note: This puzzle replaces Puzzle 1805, in which some tools were unintentionally disabled. Players may load in solutions from Puzzle 1805.
Design a binder against coronavirus! 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 sidechains at the binding site, where the spike protein normally interacts with the human receptor protein. Players can design a new protein that binds to these sidechains, blocking interactions with the human receptor. In order to bind the coronavirus target, designs will need to make lots of contacts and H-bonds with the spike protein at this 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.
Residue Count (max +550)
Penalizes extra residues inserted beyond the starting 192, at a cost of 55 points per residue. Players may use up to 202 residues in total.
Core Existence (max +2400)
Ensures that at least 28 percent of residues are buried in the core of the monomer unit.
Ideal Loops (max +500)
Penalizes any loop region that does not match one of the Building Blocks in the Blueprint tool. Use "Auto Structures" to see which regions of your protein count as loops.
SS Design (max +500)
Penalizes all CYS residues. Penalizes GLY, ALA residues in sheets. Penalizes GLY, ALA in helices.
There's a <a href=https://fold.it/portal/node/2008930">coronavirus chat</a> on 29 February in US timezones. The chat is arranged by joshmiller, and is happening on the new Foldit Discord server. This is a short notice, impromptu chat to discuss a hot new puzzle. Worst case, it's an opportunity to see what Discord offers.
You'll need a free Discord account to participate, and the chat happens 29 February at noon Eastern standard time, 09:00 Pacific standard time, or 1700 UTC/GMT/Zulu on the Foldit server.
I won't be able to participate in the Coronavirus Chat on Feb 29. Would it be possible for you to record it and post it online somewhere so I can watch it later? Video, audio, or an all-text transcript would be useful.
Like Jeff, I was out of computer reach for Corona chat. Can we get a link for those of us with time management challenges? It would be handy, and we don't say much ;)
This is an exciting puzzle. Thanks for allowing us to design proteins targeting the spike protein.
Is it possible for us to share more than 5 designs with the scientist (For instance 8 or 10 designs) ?
