1824: Coronavirus Anti-inflammatory Design

Closed since almost 6 years ago

Summary

• Created: April 10, 2020
• Expires: April 17, 2020 at 23:00 UTC
• Max points: 100

Description

Design an anti-inflammatory protein for COVID-19! 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).



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. Players can design a new protein that binds to these sidechains, blocking interactions with the 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.

Top groups

• 1. Gargleblasters 100 pts. 13,163
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• 3. Beta Folders 74 pts. 12,819
• 4. Anthropic Dreams 63 pts. 12,757
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• 7. L'Alliance Francophone 37 pts. 12,615
• 8. Hold My Beer 31 pts. 12,595
• 9. foldeRNA 25 pts. 12,476
• 10. Marvin's bunch 21 pts. 12,432

Top soloists

• 1. actiasluna 100 pts. 12,886
• 2. johnmitch 100 pts. 12,820
• 3. LociOiling 99 pts. 12,819
• 4. Crossed Sticks 98 pts. 12,808
• 5. ZeroLeak7 97 pts. 12,758
• 6. grogar7 96 pts. 12,757
• 7. Skippysk8s 96 pts. 12,750
• 8. Bruno Kestemont 95 pts. 12,749
• 9. TheGUmmer 94 pts. 12,743
• 10. Galaxie 93 pts. 12,722

Comments

[jeff101]

Are we supposed to form a disulfide bond between
cys92 on the target protein and one of the residues
on our binding protein?

[jeff101]

Are we supposed to leave the space around cys92 empty,
or should we try to fill that space with parts of our
binding protein?

[bkoep]

No, CYS 92 is not connected to anything except CYS 46 (by a disulfide bond).

Even though the CYS 92 backbone is not connected to other amino acids, it still has polar atoms. If these atoms are buried away from surrounding water, then your design should make H-bonds to those polar atoms.

It's not necessary for your design to interact with CYS 92. But since it is so close to the binding site, we expect that many designs will interact with it (and that's okay!).

[bkoep]

CYS 92 is already connected to CYS 46 by a disulfide bond, so it cannot participate in a disulfide bond with your binding protein.

[bkoep]

No, there's no need to leave empty space around CYS 92. You can fill that space with your binding protein. (But make sure to make hydrogen bonds if you bury any polar atoms!)