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1840: Coronavirus Anti-inflammatory Design: Round 4
Status: Closed


Name: 1840: Coronavirus Anti-inflammatory Design: Round 4
Status: Closed
Created: 05/20/2020
Points: 100
Expired: 05/27/2020 - 23:00
Difficulty: Intermediate
Description: Design an anti-inflammatory protein for COVID-19! This puzzle uses the new Buried Unsats Objective to detect "unsatisfied" polar atoms that cannot make hydrogen bonds with the water surrounding the protein. If your designed protein creates Buried Unsats, then it will be less likely to fold and bind to the target. (Note that this target protein includes 15 buried unsats that players may be unable to fix.) See the blog for more details about buried unsats, and for helpful tips to make a successful protein binder! Players will be unable to load solutions from previous puzzles.

Many COVID-19 complications are caused indirectly by the virus, and result from a severe over-stimulation of the human immune system. This kind of immune over-stimulation is commonly called a "cytokine storm." During a viral infection, immune cells normally release signaling proteins called cytokines, which inform the rest of the immune system about the infection and trigger inflammation. The inflammation is supposed to help the immune system fight off the infection, but too much inflammation can result in sepsis and organ failure.

One proposed strategy for treating serious COVID-19 cases is to prevent the "cytokine storm" by blocking certain cytokine signals. We want to design a protein that could block cytokine IL6, by binding to the IL6 receptor (IL6R). For more details, see our recent video update about blocking the cytokine storm.

In this puzzle, players are presented with the binding site of IL6R, which receives cytokine signals and triggers inflammation. The backbone and most of the sidechains are completely frozen, except for sidechains at the cytokine binding site. This puzzle also includes a binding helix fragment from the IL6 cytokine. 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 IL6 cytokine. In order to bind the IL6R 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.
Categories: Design, Overall

Top Groups

1Anthropic Dreams307,337100
2Go Science307,26680
4Beta Folders307,09049
5Team India307,07037

Top Evolvers

Top Soloists

1grogar7 41 66 Anthropic Dreams307,337100
2ZeroLeak7 35 16 Go Science307,26299
3NinjaGreg 23 21 Go Science307,23597
4ichwilldiesennamen 24 13  307,21096
5g_b 51 38  307,15295

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bkoep's picture
User offline. Last seen 2 hours 59 min ago. Offline
Joined: 11/15/2012
Groups: Foldit Staff

Buried Unsats (max +500)
Detects polar atoms that cannot make hydrogen bonds. Note that the frozen target includes 15 buried unsats that may be impossible to satisfy.

Residue Count (max +275)
Penalizes extra residues inserted beyond the starting 151, at a cost of 55 points per residue. Players may use up to 156 residues in total.

Core Existence (max +1000)
Ensures that at least 25 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, SER, THR in helices.

MrZanav's picture
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Joined: 12/29/2018

Is this puzzle supposed to be at a score of 177912?

bkoep's picture
User offline. Last seen 2 hours 59 min ago. Offline
Joined: 11/15/2012
Groups: Foldit Staff

Solutions from this puzzle will register extremely high Foldit scores. Usually, we try to correct the baseline score for each puzzle so that all puzzles score in the same range. But there was a mistake when we set up this puzzle, so the baseline score is much higher than normal.

This shouldn't affect gameplay or rankings. A lead of +500 pts here is equivalent to a lead of +500 pts in any other puzzle.

Joined: 09/24/2012
Groups: Go Science
Incorrect score function

303658 pts credited
Total of all subscores: -1511 pts
Total of all subscores + 8000: 6488 pts

Discrepancy: 297170 pts
Folter Bonus: 2170 pts.

On the locked protein, there are many "O points" segments, other with positive points, many with negative points.

Calculated with:


Verified with:

Moreover, I see >25 players and 9 groups with 306,XXX pts. It's quite uncomon to see players scores within top 0.3% range at start game.

OWM3's picture
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Joined: 03/08/2020
Groups: Gargleblasters

I left 4 instances for a night with 4 different recipes. And all instances crashed during the night with 3 completely different error messages.

Joined: 12/27/2012
See this feedback...

puzzle 1840 crashes and evoed solutions cannot be uploaded describes what may be a similar problem.

Right after a crash, the file log.txt in your Foldit directory may contain clues. Please consider attaching a log.txt in a reply to the feedback above. At the very least, it will identify which platform you're on.

There may also be traceback information in log.txt pointing to the source of the crash. On Windows, however, the traceback often appears to have be zeroed out.

When you restart Foldit, log.txt is overwritten, so any evidence is lost.

When you create a feedback, the Foldit website doesn't allow you to attach files. (No one knows why.) Replies to an existing feedback allow attachments, however. So you can always create a feedback, then reply to yourself with any attachments.

In addition to log.txt, the file debug.txt is sometimes generated by a crash. This file uses a properties file format, and contains the traceback and some more context. There's a timestamp and some identification of what Foldit was doing.

Unlike log.txt, debug.txt is not overwritten when you restart Foldit. It may or may not be overwritten by the next crash. Unfortunately, the debug.txt timestamp is in seconds, so it's a little hard to decipher. Check the file's creation time on your system to make sure it was created by the crash in question.

I had thought that debug.txt was supposed to be uploaded automatically, but if so, it's not clear that it's useful to the Foldit team. Still, it can't hurt to attach it to a feedback.

Joined: 12/27/2012
using multiple directories may also help...

I strongly recommend running each Foldit client from a separate directory (folder).

Multiple Foldit Clients on the wiki describes how to set this up this configuration on different platforms.

Among other things, this setup means each client will have its own log.txt (and potentially, its own debug.txt).

You also don't have to worry about the track name this way, so each client can have it's own scriptlog.default.xml and its own automatic saves in the default track.

Long long ago, the multiple directory approach seemed to reduce the number of crashes on Windows. Foldit crashed a lot in those days.

On Windows, you can just copy C:\Foldit to make c:\Foldit1, c:\Foldit2, c:\Foldit3, and so on. Then you'll need to make shortcuts to foldit.exe in each of these directories to run the clients.

I've also added custom icons for each client. See my video Running Foldit in Multiclients (for Windows) for a detailed look at the process.

grogar7's picture
User offline. Last seen 2 hours 39 min ago. Offline
Joined: 10/03/2011
no cytokine helix fragment

The puzzle description says an helix fragment from IL6 cytokine is included in the protein to be designed. That is not the case. The designable protein is presented as a denovo strand.

bkoep's picture
User offline. Last seen 2 hours 59 min ago. Offline
Joined: 11/15/2012
Groups: Foldit Staff
Good catch!

That's a mistake in the the puzzle description, which I've just edited.

Joined: 12/06/2008
Groups: Contenders
No ALA in helices?

Alanine is one of the most common AAs in helices. Why is it forbidden in helices in this puzzle?

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

Sorry I didn't see this comment before the puzzle closed!

The problem we are trying to avoid is excessive alanine. Foldit players discovered that you can pack helices really tightly using exclusively ALA. The tight packing gives really high Foldit scores, but we don't expect these designs to fold as well as designs with better "interdigitation" between sidechains in the core.

Ideally, we would put a soft limit on the amount of ALA allowed in designs (it's on our to-do list). In the meantime, we found that we can get by without ALA in secondary structure, and it seems that Foldit players can design super-stable proteins without any ALA at all.

irk-ele's picture
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Joined: 05/07/2020
Groups: None
Further Improvement

Dear scientists, just now I used "upload to scientists" to share another huge bonding improvement to my previously uploaded suggested solutions. Now, there is a total of 2/3 hydrophobic interactions (depending on which of my solutions you look at), 3 hydrogen bonds and 2 satisfied BUNS all within the target, which I think make it a very strong and possible binder.

Otherwise, as I am fairly new to this subject, I would highly appreciate it if you could have a look at it and give me feedback (Am I even on the right track?), either here or via mail or whatever possibilities there are.

Is there a place to share and discuss such topics with other players?

Thank you very much.

agcohn821's picture
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Joined: 11/05/2019
Groups: Foldit Staff

Hi Irk-ele!

Feel free to join the Foldit discord to share and discuss topics with other players and developers.
Please let me know if you have any additional questions.

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