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1823: Coronavirus ORF8 Prediction Round 2

Closed since almost 6 years ago

Novice Overall Prediction

Summary

Created
April 09, 2020
Expires
Max points
100
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!

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Comments

beta_helix Staff Lv 1

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! :-)

Artoria2e5 Lv 1

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 Lv 1

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.

beta_helix Staff Lv 1

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.

JellyJump Lv 1

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