1889: Coronavirus Anti-inflammatory Design: Round 12
|Name:||1889: Coronavirus Anti-inflammatory Design: Round 12|
|Expired:||09/17/2020 - 23:00|
|Description:||Design an anti-inflammatory protein for COVID-19! We'd like players to keep focusing on making closely-packed interfaces with no extra Buried Unsats. This puzzle prohibits SER and THR in helices, which may make it harder to satisfy BUNS, but should help the helices to fold correctly. Remember, 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 YouTube video 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. In order to bind the IL6R target, designs will need to make lots of contacts and H-bonds with the target 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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