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1968: Influenza HA Binder Design Competition
Status: Closed


Name: 1968: Influenza HA Binder Design Competition
Status: Closed
Created: 03/12/2021
Points: 100
Expired: 03/26/2021 - 23:00
Difficulty: Intermediate
Description: This puzzle is part of a special binder design competition. We are challenging Foldit players to design as many proteins as possible in this special two week puzzle. When you reach 10,000 points, submit your solution for the competition using the Upload for Scientists button, and reset the puzzle to start another submission! This puzzle is much like Puzzle 1962, with a scoring offset (a score of 10,000 here is about equivalent to 17,500 in Puzzle 1962). See the blog for more details about the competition. For players that do not wish to participate in the competition, this puzzle will also function like a regular puzzle, and will award Foldit points as usual when the puzzle expires.

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.
Categories: Design, Overall

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2Go Science10,86677
3Anthropic Dreams10,84758
5Beta Folders10,67331

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Top Soloists

1ichwilldiesennamen 16 13 Go Science10,858100
2Galaxie 4 4 Anthropic Dreams10,84798
3Enzyme 73 55 Gargleblasters10,82895
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5ucad 73 18  10,76090

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bkoep's picture
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Joined: 11/15/2012
Groups: Foldit Staff

DDG Metric (max +2000)
The predicted binding energy of your design. The goal DDG is -40.0 or less.

Contact Surface Metric (max +2000)
Measures how much of your binder surface is in close contact with the target protein. The goal Contact Surface is 400 or more.

Buried Unsats (max +500)
Penalizes 100 points for each polar atom that cannot make any hydrogen bonds.

Core Existence (max +1500)
Ensures that at least 25 percent of residues are buried in the core of the monomer unit.

Interaction Energy (max +500)
Monitors that all large PHE, TYR, and TRP residues are scoring well.

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)
Disabled use of CYS residues. Penalizes GLY, ALA residues in sheets and helices.

Joined: 12/06/2008
Groups: Contenders
Leaderboard for acceptable solutions?

Is their going to be a scoreboard posted, showing how many 10000-point solutions the players have made? After all, this is a competition, and we'd like to know how our competitors are doing. (And we like to see our names in print.)

bkoep's picture
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Joined: 11/15/2012
Groups: Foldit Staff
No realtime updates

Unfortunately, we don't have a way to update the competition status continuously in realtime. We will plan to post an interim report after the first week of the two-week competition. I may also be able to post more frequent updates here in the puzzle comments (but no guarantees!).

I agree that this is not ideal, and I wish the Foldit website were set up to show this data in real time! One of the goals of this "pilot" competition is to determine whether we should divert resources to actually implement a different reward system. That will require a non-trivial amount of work, and we don't want to demote our other priorities unless we think it will be worth it.

So far, I can tell you that nobody has submitted more than one solution!

Joined: 12/06/2008
Groups: Contenders
"Unknown" AA at position 13?

Wondering why segment 13 is "unknown", using "X" as its sidechain.

No one knows what it is? Or is it variable, and it doesn't matter what the sidechain is?


bkoep's picture
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Joined: 11/15/2012
Groups: Foldit Staff

Residue 13 is an ASN that is glycosylated, meaning that a sugar polymer is attached to the ASN sidechain after the protein is translated by the ribosome. In Foldit, the glycosylated ASN is treated like a special residue under the hood, with an undefined name and one-letter code, so it may appear as "unknown" or "X" in some Foldit tools.

See this previous comment for more details about the glycan.

Joined: 05/03/2009
Groups: Contenders
Just for a little clarity

Evening all

Can you be a little more specific, regarding what constitutes a valid 10k score. Does the chain of evidence have to include every move I make from the moment I reset and start afresh to the moment I 'submit for scientists'? Can I reload an interim quickslot if one direction didnt pan out? And what if I crash, can I rescue the last move and still be able to submit when I breach 10k?


bkoep's picture
User is online Online
Joined: 11/15/2012
Groups: Foldit Staff

Foldit will correctly handle the "chain of evidence" behind the scenes, even when Foldit crashes. Just restart Foldit and keep working with the latest autosave; you can submit this solution when it passes 10,000 points, and all of its history will remain intact.

If you have a solution with less than 10,000 points, you can undo or revert to an earlier stage of the solution and try another direction. The main thing is that you may not submit two solutions from the same restart. So, after you submit a solution with >10,000 points, you should avoid loading previous versions of that submitted solution.

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