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ztehrani's picture
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Joined: 03/29/2020
Groups: Boilermakers

Hi there-

I have students working on the coronavirus binder puzzle and we were wondering if moving the binder protein to a different region of the RBD (i.e., not in the groove) would be a feasible solution. Should we assume that any region of the provided RBD structure in gray would be accessible to the binder protein? It would help to know which segment of the RBD is provided in the puzzle, such as the residue numbers. Because if a region is buried and inaccessible to the binder, like the region with beta sheets, then I would advise students in the future to avoid this approach in their solution.

Thanks!

LociOiling's picture
User offline. Last seen 22 min 11 sec ago. Offline
Joined: 12/27/2012
locked and unlocked

In theory, a different region could work, but you have to take the puzzle setup into account.

On "Beginner Puzzle (<150): Coronavirus", most of the target (segments 1-117) is locked. In most cases, the locking covers the backbone and the sidechain. Just a few segments have unlocked sidechains. These segments are considered good binding targets.

To see the likely targets, select all segments using control + a. The segments with moveable sidechains are highlighted in blue, while the totally locked segments are gray.

The higher-numbered segments (118-200) are the designable part, where nothing is locked, and everything is possible. Select all (control + a) will always highlight these segments.

To see segment numbers, hover over a segment and hit tab. This opens the Segment Information window, which shows the segment number and amino acid, along with scoring and other information.u

Just from a player perspective, you'll have a hard time getting the locked parts in segments 1-117 to interact with your binder in 118-200.

One note from a science perspective: Foldit doesn't talk about chains. Everything just a segment, numbered from 1 to n. On "Beginner Puzzle (<150): Coronavirus", would really be chain A, residues 1-117; the binder would be chain B, residues 1-83.

A few recipes are chain aware, such as "AA Edit", https://fold.it/portal/recipe/102879, and "print protein" (aka "TMI"), https://fold.it/portal/recipe/103314. These recipes have to figure out the N- and C-terminals by looking at atom counts.

Susume's picture
User offline. Last seen 16 hours 23 min ago. Offline
Joined: 10/02/2011
Unlocked region is the target

Good question! The unlocked region of the virus protein is the spot where it binds to the ACE2 receptor on a human cell - if your students place their binder in some other location, it will be unlikely to prevent the virus from sticking to our cells.

To see what part of the sequence is modeled, your students can download the recipe called 'AA Edit 2.0.1' from the Recipes page on the Foldit website and get the sequence of the modeled portion. They can find a full sequence for the spike protein at Uniprot, and use Clustal or another alignment tool to see which portion is included in the puzzle. (I would not normally send new players to other websites for protein data, but I know Boilermakers are up to it!)

Joined: 09/24/2012
Groups: Go Science
Hi ztehrani

I made a winning solution on the first round (puzzle 1805b), but it was on the wrong side of the target. Foldit team explained why it was wrong in the blog here:
https://fold.it/portal/node/2008989

A video by Foldit team explains this in a video here at 1'20":
https://www.youtube.com/watch?v=e1YEyPX-Pqw

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