puzzle picture
1901: Coronavirus Anti-inflammatory Design: Round 14
Status: Closed

Summary

Name: 1901: Coronavirus Anti-inflammatory Design: Round 14
Status: Closed
Created: 10/08/2020
Points: 100
Expired: 10/15/2020 - 23:00
Difficulty: Intermediate
Description: Design an anti-inflammatory protein for COVID-19! This puzzle includes optional Objectives for the binder metrics. The DDG, SASA, and SC Objectives will not award any bonuses and should not affect recipes, but you can run these Objectives to check the binder metrics of your design. We've also adjusted the BUNS objective to ignore many of the "unsolvable" BUNS in the frozen target. However, there are still a few BUNS that you may not be able to satisfy. 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. 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.
Categories: Design, Overall

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bkoep's picture
User offline. Last seen 1 day 19 hours ago. Offline
Joined: 11/15/2012
Groups: Foldit Staff
Objectives

DDG Score (max +0)
The predicted binding energy of your design. The target DDG is -40.0 or less.

SASA Score (max +0)
The solvent-accessible surface area that is lost upon binding. The target SASA is 1500 or more.

Shape Complementarity (max +0)
Measures how well your binder fits the contours of the target surface. The target Shape Complementarity is 0.60 or more.

Buried Unsats (max +500)
Penalizes 60 points for each polar atom that cannot make any H-bonds. Note that the frozen target includes 3 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.

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Developed by: UW Center for Game Science, UW Institute for Protein Design, Northeastern University, Vanderbilt University Meiler Lab, UC Davis
Supported by: DARPA, NSF, NIH, HHMI, Amazon, Microsoft, Adobe, RosettaCommons