1834: Coronavirus Anti-inflammatory Design: Round 3
|Name:||1834: Coronavirus Anti-inflammatory Design: Round 3|
|Expired:||05/13/2020 - 23:00|
|Description:||Design an anti-inflammatory protein for COVID-19! The starting structure is a design by Bruno Kestemont from Puzzle 1824, as featured in our latest video Lab Report #8. Players may work to try and improve the starting structure, but also have the freedom to redesign binder from scratch. The best designs will have lots of helix or sheet structure, with a large core of orange hydrophobics. See our previous blog post for tips about designing a successful binder! Players may not load in 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.
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