puzzle picture
1823: Coronavirus ORF8 Prediction Round 2
Status: Closed

Summary

Name: 1823: Coronavirus ORF8 Prediction Round 2
Status: Closed
Created: 04/09/2020
Points: 100
Expired: 04/16/2020 - 23:00
Difficulty: Novice
Description: This is a follow-up to Puzzle 1820, but this time we are providing you with a starting model. Players may load in previous work from Puzzle 1820. This protein is encoded in the viral genome of SARS-CoV-2, but the protein's structure is still unknown. If we knew how this protein folds, we might be able to figure out its exact function. Refold this starting model to find higher-scoring solutions, which will tell us how this protein is most likely to fold!
Categories: Overall, Prediction

Top Groups

RankGroupScorePoints
1Anthropic Dreams10,825100
2Go Science10,77087
3Beta Folders10,67474
4Gargleblasters10,63964
5Void Crushers10,61454

Top Evolvers

Top Soloists

RankPlayerGroupScorePoints
1grogar7 83 2 Anthropic Dreams10,812100
2Xartos 20 14 Go Science10,729100
3LociOiling 8 3 Beta Folders10,67499
4Wilm 117 4648 Go Science10,66798
5Aubade01 117 55  10,63497


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Comments

Joined: 06/06/2013
Groups: Gargleblasters
protein sequence

mkflvflgiittvaafhqecslqsctqhqpyvvddpcpihfyskwyirvgarksaplielcvdeagskspiqyidignytvsclpftincqepklgslvvrcsfyedfleyhdvrvvldfi

if this helps those of you who can do overlays well

Joined: 06/06/2013
Groups: Gargleblasters
SS given

LHHHHHHHHHHHHHHHHLLLLHHHHHHLLLLLLLLLHHHLLLLLLEEEEEEELLEEEEEEELLLLLLEEEELLEELLLLEELLLLLLLLLLLLLLLEEEEEEEEEELLLEEEEEEEEEELL

grogar7's picture
User offline. Last seen 1 hour 51 min ago. Offline
Joined: 10/03/2011
Players may load results from the previous ORF8 puzzles

It would be a good idea to let folks know about this option from the start. I will post in chat and Discord.

LociOiling's picture
User offline. Last seen 1 hour 35 min ago. Offline
Joined: 12/27/2012
Groups: Beta Folders
Not sure it was intentional....

You can load a solution from 1820, but you can't use it for "load as guide".

Joined: 05/09/2008
Groups: None
Thanks for pointing this out

I'll look into why "load as guide" isn't working.

grogar7's picture
User offline. Last seen 1 hour 51 min ago. Offline
Joined: 10/03/2011
Loading builds from prior puzzle?

Why would the development team allow players to load builds from puzzle 1820 into this puzzle? Are you looking for refinements to those prior builds, or do you really want us to start with the structure you have presented?

Wouldn't it tend to stifle the competition if I load my high scoring build from 1820?

Thanks,
grogar7

Joined: 05/09/2008
Groups: None
Thanks for the reminder!

I added this info to the puzzle description.

This starting topology is just a suggestion, as we have no idea how correct/incorrect it is.

However, we can imagine players modifying their previous predictions based on this model... or even creating hybrids between the two (which is why I want to fix the "load as guide" issue).

Joined: 09/19/2011
Groups: None
Signal peptide

Sorry if this is a naive question; is it known whether the first 15 AA are a signal peptide that is cleaved off in the actual protein?

Joined: 05/09/2008
Groups: None
Good question!

Since we do not know the structure of this protein, we can only speculate.

I did run it through a Signal Peptide Prediction Server, SignalP-5.0, and indeed that was the prediction:
http://www.cbs.dtu.dk/cgi-bin/webface2.fcgi?jobid=5E907DFF00006C758F0CC973

Joanna_H's picture
User offline. Last seen 15 hours 57 min ago. Offline
Joined: 12/29/2010
Groups: Gargleblasters
Starting Model

The starting model provided looks just like the one PSPRED indicated, I was wondering why it looked so similar to my last attempt... http://bioinf.cs.ucl.ac.uk/psipred/&uuid=3c238016-7823-11ea-b4c4-00163e100d53

Joined: 05/09/2008
Groups: None
PSIPRED is very popular!

It is likely that most people used the PSIPRED predictions we posted for the last puzzle:
https://fold.it/portal/node/2009337#comment-40823

jeff101's picture
User offline. Last seen 15 hours 26 min ago. Offline
Joined: 04/20/2012
Groups: Go Science
Cysteines in Puzzles 1820 & 1823

Since this puzzle has the same sequence as in Puzzle 1820:
https://fold.it/portal/node/2009337
should we still expect none of its 7 cysteines to form
disulfide bonds? Should we also expect all 7 of its
cysteines to be on the protein exterior?

Joined: 05/09/2008
Groups: None
Again, this is a tough one.

As we don't know the structure of this protein, we really can only speculate.

I did run it through a Disulfide Bonding State Prediction Server, DISULFIND, and indeed it predicts 3 disulfide bridges (with 58.9% confidence):
http://disulfind.dsi.unifi.it/monitor.php?query=H0o2y1

I was to reiterate, however, that all these tools: DISULFIND, SignalP-5.0, and even PSIPRED, are all just statistical predictions... they are often correct, but are sometimes very wrong.

Proteins tend to follow their own rules, and they love creating exceptions (I learned this the hard way when studying knotted proteins for my PhD! :-)

Joined: 01/19/2019
Groups: Go Science
In line with the 25,83 37,90

In line with the 25,83 37,90 topology, some article on bioRxiv says this is gonna be an Ig fold:

mkflvflgiittvaafhqecslqsctqhqpyvvddpcpihfyskwyirvgarksaplielcvdeagskspiqyidignytvsclpftincqepklgslvvrcsfyedfleyhdvrvvldfi
lllllllllllllllllleeeeeeeellleeeeelllllleelllllllleeeeelleeeelllllllllleeelllleeeeelleeeeelllllleeeeeeeelllllllllllllllll
                                    |37------------------------------------------------90|
                        |25-----------------------------------------------------83|

No idea about 61,102 though. My hunch is that it is possible, since this pair only occurs in the SARSr-CoV insertion.

https://www.biorxiv.org/content/10.1101/2020.03.04.977736v1.full

Wilm's picture
User offline. Last seen 21 weeks 3 days ago. Offline
Joined: 02/28/2013
Groups: Go Science
Signal peptide cleavage

If the N-terminus is a signal peptide and if it is cleaved, wouldn't it be useful to post the puzzle at some point without the first 15aa? Even if there is no cleavage, the N-term will be in the membrane, so in Foldit any solution separating that helix from the rest of the fold will score horribly and players will be less likely to follow solutions like that.

Joined: 05/09/2008
Groups: None
Good suggestion!

That is a very good suggestion, Wilm.

We do have to keep in mind that we cannot be 100% sure that the N-terminus is a signal peptide, it's not like we have a cryo-EM map to work off of, we just have the sequence.

We'll definitely consider posting a trimmed version of it, if we end up running another puzzle for this protein... as there are many SARS-2-CoV protein sequences with no experimental structure available.

Joined: 09/22/2017
Groups: Beta Folders
Reply

The Diamond Light Source in the UK has switched into emergency mode - if somebody can crystallize the ORF8 with and wit out the signal peptide and has good ties to DLS we could get fast turnover XRC

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