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1898: Coronavirus Binder Design: Round 19
Status: Closed

Summary

Name: 1898: Coronavirus Binder Design: Round 19
Status: Closed
Created: 10/01/2020
Points: 100
Expired: 10/08/2020 - 23:00
Difficulty: Intermediate
Description: Design a binder against coronavirus! 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. Remember, if your designed protein creates Buried Unsats, then it will be less likely to fold and bind to the coronavirus target. (Note that this target protein includes 3 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 may not load solutions from previous puzzles.

In late 2019, a new highly-infections virus emerged out of Wuhan, China. This virus belongs to the coronavirus family, and is similar to the virus that caused the SARS epidemic in 2002. Coronaviruses display a "spike" protein on their surface, which binds tightly to a receptor protein found on the surface of human cells. Once the coronavirus spike binds to the human receptor, the virus can infect the human cell and replicate. In recent weeks, researchers have determined the structure of the 2019 coronavirus spike protein and how it binds to human receptors. If we can design a protein that binds to this coronavirus spike protein, it could be used to block the interaction with human cells and halt infection!

In this puzzle, players are presented with the binding site of the coronavirus 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 coronavirus target, designs will need to make lots of hydrophobic contacts and H-bonds with the flexible sidechains at the 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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Comments

bkoep's picture
User offline. Last seen 1 day 20 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 +320)
Penalizes 60 points for each polar atom that cannot make any hydrogen bonds. Note that the frozen target includes 3 buried unsats that may be impossible for players to satisfy.

Residue Count (max +275)
Penalizes extra residues inserted beyond the 177, at a cost of 55 points per residue. Players may use up to 182 residues in total.

Core Existence (max +2400)
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)
Disabled use of CYS residues. Penalizes GLY, ALA residues in sheets. Penalizes GLY, ALA in helices.

Joined: 06/24/2008
Groups: Void Crushers
Bug in objectives

Bug in objectives: it keeps losing the score. I have restarted both the app and my computer.
Predev MAC

APPAAP's picture
User offline. Last seen 2 hours 58 min ago. Offline
Joined: 04/25/2020
Groups: None
Matrices objectives vs Highest score achieved

I noticed that some of mine solutions in this puzzle with the highest achieved scores does not guarantee best achieved Matrices DDG, SASA and SC. Is this the case? I have read in the blog pages that the new foldit update will try to handle this. As far I understand the docking or binding of the protein to the target may play an important role in SC and DDG but the overall design has to do more with the SASA and therefore higher SASA may related more to the number of protein segments availiable that can cover the binding site. Is this correct or I am loosing something? On the other hand achieving a high score is more or less the design of a good protein core as starting point.

APPAAP's picture
User offline. Last seen 2 hours 58 min ago. Offline
Joined: 04/25/2020
Groups: None
Metrics objectives vs Highest score achieved

Correction. Metrics is then correct not Matrices!

bkoep's picture
User offline. Last seen 1 day 20 hours ago. Offline
Joined: 11/15/2012
Groups: Foldit Staff
Metrics do not contribute to score

You're correct that a high score in this puzzle does not guarantee good DDG, SASA, or SC. Those metrics are separate from your score.

We would like to include these metrics in the Foldit score (so that designs with good DDG, SASA, and SC have higher scores), but they are very slow to compute and that raises some technical challenges we have to resolve. Soon we will release an update so that these metrics can add bonus points to your Foldit score!

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