puzzle picture
1923: MERS-CoV Binder Design: Round 6
Status: Closed

Summary

Name: 1923: MERS-CoV Binder Design: Round 6
Status: Closed
Created: 11/27/2020
Points: 100
Expired: 12/04/2020 - 23:00
Difficulty: Intermediate
Description: Design a binder for the viral spike of MERS-CoV! This puzzle does not use the new Contact Surface Objective and is more similar to the previous Round 4 puzzle, except that the Metrics bonuses have been scaled down significantly. 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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Comments

bkoep's picture
User offline. Last seen 1 day 13 hours ago. Offline
Joined: 11/15/2012
Groups: Foldit Staff
Objectives

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: 05/19/2009
Groups: Contenders
Reloading previous version ?

In round 5 it said "Once we find and fix the bugs, we intend to repost the puzzle so that players may load previous work and continue competitive play. " But I cannot reload the revious work. Is this intentional ?

bkoep's picture
User offline. Last seen 1 day 13 hours ago. Offline
Joined: 11/15/2012
Groups: Foldit Staff
Bug in Contact Surface

Sorry, we should have been more clear. The bug from Round 5 seems to be related to the Contact Surface Objective, and we are still tracking it down. It will probably be a couple of weeks before we are able to fix the problem and repost Round 5 with Contact Surface again.

Since Round 5 used Contact Surface (instead of SASA and SC), we want to make sure the reposted version also uses Contact Surface. In the meantime, we will continue to run puzzles like this one, with SASA and SC instead of Contact Surface.

Joined: 05/19/2009
Groups: Contenders
Thank you for clarifying !

Thank you for clarifying !

Joined: 06/24/2008
Groups: Void Crushers
Wiggle strangeness

Wiggle seems to lag on starting.
Lagging so much a few times that I thought it wasnt working; but then started.
MAC
PreDev

Joined: 12/06/2008
Groups: Contenders
Error in SC calculation

There is a bug in the scoring of the SC metric. Using the latest "main" release.

The value should go from 0 to 1.00, but mine is 8.14 x 10^265. My protein isn't even close to the target.

(I wanted to write out that number without using scientific notation, but I figured everyone would not want to see 265 zeroes.)

Photo here:

https://ibb.co/kHHd7L1

Joined: 06/24/2008
Groups: Void Crushers
Scoring Bug

Just got my first scoring error on 1923. My high score is on my graph but cmd b brings up a lower score.

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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, Boehringer Ingelheim, RosettaCommons