Placeholder image of a protein
Icon representing a puzzle

1852: Coronavirus Anti-inflammatory Design: Round 6

Closed since over 2 years ago

Intermediate Overall Design

Summary


Created
June 17, 2020
Expires
Max points
100
Description

Design an anti-inflammatory protein for COVID-19! This puzzle is very much like our Round 5 Anti-inflammatory puzzle, but we've relaxed the restrictions on SER and THR in helices. The Buried Unsats Objective will not award any bonus or penalty points, but you can still use it 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. 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.

Top groups


  1. Avatar for Anthropic Dreams 100 pts. 11,880
  2. Avatar for Gargleblasters 2. Gargleblasters 74 pts. 11,830
  3. Avatar for Go Science 3. Go Science 54 pts. 11,783
  4. Avatar for Contenders 4. Contenders 38 pts. 11,767
  5. Avatar for Beta Folders 5. Beta Folders 27 pts. 11,737
  6. Avatar for Void Crushers 6. Void Crushers 18 pts. 11,584
  7. Avatar for Marvin's bunch 7. Marvin's bunch 12 pts. 11,396
  8. Avatar for BOINC@Poland 8. BOINC@Poland 8 pts. 11,257
  9. Avatar for L'Alliance Francophone 9. L'Alliance Francophone 5 pts. 11,228
  10. Avatar for Hold My Beer 10. Hold My Beer 3 pts. 11,071

  1. Avatar for Deleted player pts. 11,873
  2. Avatar for Mike Lewis 2. Mike Lewis Lv 1 98 pts. 11,810
  3. Avatar for Bruno Kestemont 3. Bruno Kestemont Lv 1 96 pts. 11,751
  4. Avatar for Xartos 4. Xartos Lv 1 94 pts. 11,740
  5. Avatar for LociOiling 5. LociOiling Lv 1 92 pts. 11,737
  6. Avatar for grogar7 6. grogar7 Lv 1 90 pts. 11,717
  7. Avatar for silent gene 7. silent gene Lv 1 88 pts. 11,688
  8. Avatar for ichwilldiesennamen 8. ichwilldiesennamen Lv 1 86 pts. 11,688
  9. Avatar for Joanna_H 9. Joanna_H Lv 1 84 pts. 11,686
  10. Avatar for mirp 10. mirp Lv 1 82 pts. 11,678

Comments


bkoep Staff Lv 1

Buried Unsats (max +0)
Detects polar atoms that cannot make hydrogen bonds. Note that the frozen target includes 15 buried unsats that may be impossible to satisfy. This Objective awards no bonus or penalty.

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 in helices.