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1886: Coronavirus Binder Design: Round 17
Status: Closed

Summary

Name: 1886: Coronavirus Binder Design: Round 17
Status: Closed
Created: 09/03/2020
Points: 100
Expired: 09/10/2020 - 23:00
Difficulty: Intermediate
Description: Design a binder against coronavirus! The new metrics have been left out to preserve regular recipe performance, but other Objectives are still in effect. 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 8 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

Joined: 09/29/2016
Groups: Gargleblasters
Slim chance but... (Repurposing this post)

These Objectives were taken from the last Corona Binder round. (I'm assuming the BUNS metric hasn't changed in terms of points and such)
Note: Threonine and Serine are once again allowed in Helices.

Objectives>

Buried Unsats (max +20)
Penalizes 60 points for each polar atom that cannot make any hydrogen bonds. Note that the frozen target includes 8 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.



ORIGINAL POST IS BELOW

Is it possible to have an 1886b, where the New Metrics ARE enabled, for those of us who'd much rather have the New Metrics and deal with any slowness imposed to recipes?
(Having to use Recipes with their "Disable Slow Filters" option turned off, I'd bet is still faster than having them toggle filters and doing Run All so often!)
[EDIT: User nspc (@pc on Discord) suggested something that I quite liked the idea of, as to not leave anyone out -- have this "sister puzzle" be able to load our saves from the main 1886, and vice versa! That would allow us to hand-fold on the New Metrics version, and run Recipes on the other puzzle. An actual "Have your cake and eat it too" :) ]

Primarily, because I feel like I'm just wasting time by working on another design that I won't be able to load back in when the New Metrics are finally re-added :\
However, if we WILL be allowed to load in all our old designs, to go back over and improve them if we want... then it wouldn't be a waste.

Thanks!
-Form

nspc's picture
User offline. Last seen 5 hours 12 min ago. Offline
Joined: 03/26/2020
Groups: Go Science
good idea

That a good idea. And we can have the possibility to share saves between 1886 and 1886b.
And compare the differences !

It can be very interesting to have a score system in new metrics with 1886b, to experiment how a new heuristic can help recipes.

And get better solutions that works more in labs !

bkoep's picture
User offline. Last seen 1 hour 41 min ago. Offline
Joined: 11/15/2012
Groups: Foldit Staff
Great suggestions

I like these ideas, but unfortunately we can't edit a puzzle that is already posted (like this one). So there is no way to enable sharing from another puzzle.

I don't like the idea of an alternate puzzle (with no sharing), because we don't want to split the community effort between two puzzles.

We should have an update soon so that we can use the new metrics properly!

Joined: 09/29/2016
Groups: Gargleblasters
Thanks :)

I think we all agree on the inability to share between the two puzzles would not be conducive, or fair.

Though, by re-launching 1886 as, say 1886b and then along side it put up 1886b2 (with the metrics), that'd accomplish it by then letting current progress carry over wouldn't it? (Not to push, but just as a last-ditch effort! lol)

Thanks again, looking forwards to being able to use the New Metrics again, in any capacity :)
-Form

Joined: 09/24/2012
Groups: Go Science
Round 2 with new metrics, load old solutions

It would allow us to screen our present solutions with the new metrics.
And to experiment if it's better to focus on new metrics from start or late game.

nspc's picture
User offline. Last seen 5 hours 12 min ago. Offline
Joined: 03/26/2020
Groups: Go Science
extra hydrophobic metric

With some recipes, player protein have often too much hydrophobics in contact zone, and doens't fold correctly in lab after.

Maybe we need a metric that compare score when protein is detached too?

But a simple metric can just be a "hydrophobic sidechain couter outside the player protein" (ignoring the target protein). And add penalty for each extra hydrophobics outside.

I think it can be a fast compute metric.

Do you think it can help?

nspc's picture
User offline. Last seen 5 hours 12 min ago. Offline
Joined: 03/26/2020
Groups: Go Science
SASA and SC

SASA and SC are fast metrics. Only DDG is slow.

Do you think we can have only SASA or SC with score in next puzzle?

SASA looks to be very important, because recipes we use (like GAB) often find higher score when protein is detached (because that often resolve BUNS).
We can fix it in each iterations with hand folding of course. But We can lose a good solution during the recipe is running, because the score was lower, and it saved only a best score.

Lot of our high score solutions have a SASA problem just because it is not inclued in puzzles. In the LBC1 the top score solutions of my group are :
More hydrophobics, some additional voids and lower SASA.
(But there is less BUNS, and something maybe cleaner ^^).

Maybe in design puzzles, one of the most important thing is to choose the best zone.
In LCB1 I saw that there is a good contact zone where there is lot of hydrophobics. And the contact surface area is maximized, keeping very good protein ideality.

Joined: 09/29/2016
Groups: Gargleblasters
Hmmm

I still envision there'd be a huge time penalty with how Foldit is currently coded for calculating Objectives, if even ONE of those 3 New Metrics were allowed to calculate in real time so that it could give us a score <_>
But 2 of them getting scored would induce a huge slowdown (to the point lots of people would stop folding).

However, I guess it MIGHT be possible for it to Score, but still be user-triggered (the need to click Run All), if those metrics only gave a Positive bonus (no negatives, like BUNS). Also where its scale was significant enough where the 'better' the metric was, the bigger the bonus became. That way you would DEFINITELY want to make sure you occasionally calculated it in order to improve your score...

Keep in mind this would be solely as a stop-gap and not how I'd expect them to be once the "real-time calculation" system gets figured out... But it'd have to be rather "extreme" (absurd) in order to entice players to run them!

I think maybe a bonus of 500 points for every 10 with SASA -- therefore, a SASA value of 1500 would deliver a Bonus of 75000 points.

For SC, that's the harder one I think, where it'd have to be around 100 points for every thousandths increase in SC -- so an SC of 0.611 would deliver a Bonus of 61100 points.

Granted, this could also be scaled back, but then our protein's un-filtered score would need to be dialed back, too. The entire point here is to exploit our brain's desire to "be the best", which comes down to ranking higher. And since points are completely irrelevant for everything except to guide us, the scale assigned to them doesn't matter. (Case in point, that Anti-Inflamm puzzle where there was an oops and we were in the 300K score range :P)

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