Fold this coronavirus protein! This is one portion of a larger protein encoded in the viral genome of SARS-CoV-2. It is encoded in a region of the genome called NSP2, but the protein's structure and function are still unknown. If we knew how this protein folds, we might be able to figure out its exact function. The puzzle's starting structure shows SS predictions from PSIPRED, and hints which parts of the protein might fold into helices or sheets. Refold this protein to find high-scoring solutions, which will tell us how this protein is most likely to fold!
"Disulfide connectivity
For each pair of cysteine in the input sequence,
a neural network trained to recognize disulfide bonds
produce a score ranging from 0 to 1 (higher the score,
higher the prediction reliability)."
It also gives an example with 4 cysteines and
6 possible disulfide bonds with scores ranging
from 0.1 to 0.9. It picks 2 disulfide bonds each
with a score of 0.8 as the best combination.
DB_state predicted disulfide bonding state (1=disulfide bonded, 0=not disulfide bonded).
DB_conf confidence of disulfide bonding state prediction (0=low to 9=high).
So I guess it predicts that no disulfide bonds form,
but it is not very confident in this prediction.
Any ideas why this 140 residues section of the NSP2 protein is not buried inside the other 498 residues of NSP2 protein?
We cannot ignore hydrophobicity in Foldit, so best strategy to have top score on this puzzle seems to be skipping any secondary structure prediction and even the real protein SS and build your own.
My understanding is the CASP organizers have tentatively divided the larger viral proteins into smaller sections (domains) based on the predictions they got back in the first round of competition. Those predictions came from both servers and human teams.
Ok, now it became a bit clearer why do we have residues 360-499 of the NSP2 protein. That looks like a domain of the highest distance similarity between different CASP models. And that part has the highest helix propensity according to the SS prediction.
But I still cannot see any evidence that this fragment is spatially separated from the rest of the NSP2 protein to search its highest Foldit score. The Hiding score looks important enough to skip any structure trying to hide hydrophobics of this NSP2 fragment inside itself.
That's right, Serca. We are simply going off of suggestions from the CASP organizers about tentative domain assignments of this target.
These suggestions likely come from inter-residue distance prediction models, similar to AlphaFold. As far as I know, nobody has collected any empirical data about this protein's structure. So, this sequence might form a well-folded domain; but it might not. Foldit predictions might help us figure that out!
