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1926: MERS-CoV Binder Design: Round 7
Status: Closed


Name: 1926: MERS-CoV Binder Design: Round 7
Status: Closed
Created: 12/04/2020
Points: 100
Expired: 12/11/2020 - 23:00
Difficulty: Intermediate
Description: Design a binder for the viral spike of MERS-CoV! We really liked some of the top-scoring solutions coming out of the previous Round 6 puzzle, and this puzzle is set up the same way. In this puzzle, the Metrics have a ramped bonus; as you improve DDG, SASA, and SC, you will get an increasing bonus until you reach the threshold of DDG < -40, SASA > 1500, and SC > 0.6, and then the bonus will be capped. Remember that Metrics are slow to compute and run in the background, so gameplay may be different from regular puzzles. See the blog for more info about Foldit Metrics.

MERS is a respiratory disease similar to COVID-19, and is caused by a related coronavirus. There have been several MERS outbreaks since 2012, but there is still no treatment has been developed for the disease. The MERS-CoV virus is coated with a spike protein that recognizes the human protein DPP4, which is found on the surface of lung cells. A protein that binds to the MERS-CoV spike could be used as a drug to block DPP4 recognition and slow viral infection.

In this puzzle, players are presented with the binding site of the MERS-CoV spike protein. The backbone and most of the sidechains are completely frozen, except for flexible sidechains at the binding site, where the spike protein normally interacts with the human receptor protein. Players can design a new protein that binds to these sidechains, blocking interactions with the human receptor. In order to bind the MERS-CoV target, designs will need to make lots of hydrophobic contacts and satisfy any polar atoms that are buried at the interface. 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 16 min 10 sec ago. Offline
Joined: 11/15/2012
Groups: Foldit Staff

Buried Unsats (max +500)
Penalizes 60 points for each polar atom that cannot make any hydrogen bonds.

Residue Count (max +275)
Penalizes extra residues inserted beyond the starting 161, at a cost of 55 points per residue. Players may use up to 166 residues in total.

Core Existence (max +1500)
Ensures that at least 25 percent of residues are buried in the core of the monomer unit.

Interaction Energy (max +500)
Monitors that all large PHE, TYR, and TRP residues are scoring well.

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)
Disabled use of CYS residues. Penalizes GLY, ALA residues in sheets. Penalizes GLY, ALA in helices.

SASA Metric (max +100)
The solvent-accessible surface area that is lost upon binding. The target SASA is 1500 or more.

DDG Metric (max +100)
The predicted binding energy of your design. The target DDG is -40.0 or less.

SC Metric (max +100)
Measures how well your binder fits the contours of the target surface. The target Shape Complementarity is 0.60 or more.

Joined: 09/29/2016
Groups: Gargleblasters

I'm wondering if it may not be better to mark DDG, SASA, and SC 'Disabled' again (like it was originally), instead of having even the minuscule bonus, considering the bonus for them ""doesn't work"" as intended? (Provided that CS still isn't fixed by next round)

My thought is --and this is where it's speculation-- that considering the fact that they are not being included in the Undo History, having them disabled again would solve:
-- The "Restore Best" Tools not restoring their respective actual bests. (Thereby alleviating frustration, but also letting Recipes work as intended.)
-- Allow for Evolving to be less confusing for those who aren't aware of what's going on. (To those that don't, you need to disable only your DDG, SASA, SC filters to see the score that everything is working from.)
-- Keep from Undo Points from being overwritten while hand folding, which is caused by various different things... that I unfortunately haven't quite nailed down. ([sorta] Good news is I determined it's a core Foldit issue, not Metrics related; the Auto-Calc method just easily/automatically creates the base scenario to make it easy to encounter.)

Plus, then there's nothing extra to calculate, meaning things can run faster.

Just some food for thought :)

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