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.
Buried Unsats (max +100)
Penalizes 60 points for each polar atom that cannot make any H-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.
Yesterday I ran a script to try and evo a teammates solution which had a score of 11583. The script crashed after a bit apparently without registering any gain and I then logged off.
This morning, to my surprise, I see I'm registered on the website as having evod with a score of 11763. Looking at my local Evolver solutions, it seems the Recent Best and Very Best solutions remain at 11583, and yet there is a Quicksave Evolver Solution 23 with a score of 11680. When I try to load this last solution however (and after running Filters) it gives a score of 11440 and says I've evo'd.
All rather confusing. I've scientist-shared The Quicksave solution.
It's usefull and relatively easy to use. But it would be VERY usefull if the metrics would be awarded a (numerical) 0.000001 x metrics bonus.
With this small bonus correlated with the metrics, we could create different scripts in order to optimize our solutions (from the scientist's point of view) without influencing the competition score.
I hope that this is possible without compromizing the loading back into the competition puzzle (because still many of us are more competing than purely working for science).
