1910: MERS-CoV Binder Design: Round 2

Closed since over 5 years ago

Summary

• Created: October 29, 2020
• Expires: November 05, 2020 at 23:00 UTC
• Max points: 100

Description

Design a binder for the viral spike of MERS-CoV! This puzzle is similar to Puzzle 1907, but now includes special Foldit Metrics for the DDG, SASA, and SC of your solution. These Metrics are slow to compute and run in the background, so gameplay may be different from regular puzzles. Each Metric has a target, players will receive a 1000 pt bonus for meeting each target. 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.

Top groups

• 1. Go Science 100 pts. 17,540
• 2. Gargleblasters 73 pts. 17,536
• 3. Anthropic Dreams 52 pts. 17,358
• 4. Contenders 36 pts. 17,209
• 5. Hold My Beer 24 pts. 16,816
• 6. BOINC@Poland 16 pts. 15,804
• 7. Void Crushers 10 pts. 15,130
• 8. Marvin's bunch 6 pts. 15,090
• 9. Beta Folders 4 pts. 15,020
• 10. L'Alliance Francophone 2 pts. 14,574

Top soloists

• 141. mwm64 1 pt. 0
• 142. Deleted player 1 pt. 0
• 143. LtKowalski 1 pt. 0
• 144. Guillaume628 1 pt. 0
• 145. aznarog 1 pt. 0
• 146. aspadistra 1 pt. 0
• 147. devjosh 1 pt. 0
• 148. Friedo12345 1 pt. 0
• 149. cbwest 1 pt. 0
• 150. InfoManiac742 1 pt. 0

Comments

[bkoep]

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 +1000)
The solvent-accessible surface area that is lost upon binding. The target SASA is 1500 or more.

DDG Metric (max +1000)
The predicted binding energy of your design. The target DDG is -40.0 or less.

SC Metric (max +1000)
Measures how well your binder fits the contours of the target surface. The target Shape Complementarity is 0.60 or more.

[g_b]

1) under Soloist Competition in upper right of screen it says 14101 position 26
2) in Auto save screen the top score is 13366 and same when I do Restore Very Best
3) on the puzzle page it says portion 34 with a score of 13479

can't get back to the 14101

[Formula350]

This was something I documented in the filters on the "Coronavirus Binders with Metrics Sandbox" puzzle a week ago, and had hoped would get fixed before they rolled those filters out into a Science puzzle. Alas, it was not :(

I let the team know, though, don't worry! Hopefully a 1910b will come out with the issue fixed.

[APPAAP]

First I want to thanks bkoep for answering in the Foldid puzzle Coronovirus Binder Metrix Sandbox. Secondly I found this version of Metrics useful although not easy-convenient (I mean the degree of easiness for playing )relative to previous versions but on the other hand this may help to find better solutions.

Now I am starting understand that in the previous foldit versions high score not necessary means a valuable solution. Only a low energy of protein does not guarantee stabiliy is it that right?

As far I can understand Enzyme and ZeroLeak7 may have about 99% propability in their designs to be real implemented compared to about 66% of mine. The 1% missing can make a big difference in the evolution of a protein folding. Metrics may show the way but I do not know how well the design will correspond to the real protein build up.
I would like to have a penny four your thoughts i.e. if are you using recipes for getting high scores? I am a relative new player to foldit and may need to join some group. Personally I try some of other players recipes but I do not use any.
I also noticed as g_b states that you can get back the highest score achieved. This probably is not due to the buggy metrices but rather because when you disable them you get the highest score which happen not to be the total highest with the metrices. Anyway you cannot get back the best solution if you proceed with matrices may foldit team has to take care.

[Bletchley Park]

Here is the link to the original bug report that I submitted:

https://fold.it/portal/node/2010614