Foldit

1811: Coronavirus Binder Design: Round 3

Closed since about 6 years ago

Intermediate Intermediate Overall Overall Design Design

Summary

Created: March 12, 2020
Expires: March 19, 2020 at 23:00 UTC
Max points: 100

Description

Design a binder against coronavirus! This is Foldit's third coronavirus puzzle, which challenges players to design an antiviral protein that could bind to the 2019 virus and disrupt viral infection. This puzzle provides a helix fragment that is already known to bind to the coronavirus, and Foldit players can design a new protein that includes this fragment. Players should focus on building up a protein with a large core of orange hydrophobics, and the best designs will also make additional contacts with the target. See our latest video update or the Foldit blog for tips about designing a successful binder! Solutions from previous puzzles are incompatible with this puzzle, so players may NOT load in previous work.

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. This puzzle also includes helix fragment from the human receptor. Players can fold and design about 55 residues flanking the binding helix, with the goal of creating a well-folded protein that can bind the target in the same way as the human receptor. Final designs will need to make additional hydrophobic contacts and H-bonds with the flexible sidechains at the target 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.

Top groups

21. Trinity Biology 2 pts. 11,537
22. Australia 2 pts. 11,214
23. Team China 1 pt. 11,091
24. Mojo Risin' 1 pt. 11,085
25. Minions of TWIS 1 pt. 9,766
26. Coastal Biochemistry 1 pt. 9,191
27. Covid19Busters 1 pt. 6,398
28. MSc UoB test1 1 pt. 0
29. DSN @ Home 1 pt. 0
30. Team Canada 1 pt. 0

241. Prodigal_V Lv 1 42 pts. 12,486
242. pfirth Lv 1 41 pts. 12,469
243. moep Lv 1 41 pts. 12,468
244. wackadoo Lv 1 41 pts. 12,457
245. fatimakhan222222 Lv 1 41 pts. 12,440
246. monkry Lv 1 41 pts. 12,437
247. Origami314 Lv 1 41 pts. 12,429
248. MaciekB Lv 1 40 pts. 12,415
249. kevin everington Lv 1 40 pts. 12,401
250. Joeshmoe7312 Lv 1 40 pts. 12,391

Comments

jeff101 Lv 1

March 16, 2020

We're getting closer to an updated "print protein" recipe, and I noticed an interesting discrepancy.

In 1811, if you hover over segment 1 and hit "tab", it shows the segment score as "-0.0". While it's not clear how -0 differs from 0, that's fine.

If you enter this one-line recipe and run it:

print ( current.GetSegmentEnergyScore ( 1 ) )

the result is non-zero:

-16.759085881012

Segment 2 is similar, showing a zero score in the segment information window, but reporting a score of 50.183449869801 using the recipe.

Just for the sake of completeness, if you run current.GetSegmentEnergySubscore for all subscores, you get zero. This little recipe demonstrates:

SEG = 2

tscore = current.GetSegmentEnergyScore ( SEG ) 
    
print ( "total score for segment " .. SEG .. " = " .. tscore )

local Subs = puzzle.GetPuzzleSubscoreNames ()

local tsubs = 0
for ii = 1, #Subs do
    local subscore = current.GetSegmentEnergySubscore ( SEG, Subs [ ii ] )
    print ( "score part " .. Subs [ ii ] .. ", score = " .. subscore )
    tsubs = tsubs + subscore
end
print ( "total of all subscores for segment " .. SEG .. " = " .. tsubs )

The nice part is that when you total up a bunch of -0 scores, you get plain old 0.

It's not clear to me why the segments with all zero subscores still report a score. It may have something to do with keeping the different versions of the score consistent, or it may just be a glitch. We've probably been seeing similar results on other, similar puzzles like the aflatoxin series, but I haven't gone back to check.

Anyway, this is for jeff101 and anyone else who likes to explore the boundaries. The new print protein will have a couple of new columns to highlight issues of this type. Worst case, you'll have all the numbers, and can add them up as you see fit.

Susume Lv 1

March 17, 2020

I just noticed last night that in the blueprint tool, above the row of letters, there is a checkbox for ABEGO colors. If you uncheck it, the letters in the blueprint tool will be colored the same as your protein, and you can see which ones are gray (locked) and which are bright (unlocked).

Susume Lv 1

March 17, 2020

Here's the video (edited for length and clarity, thanks ianh!) of my stream from March 14, talking about corona virus strategy and also one method of approaching the permanent cutpoints.