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.
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.
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.
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.
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.
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.
