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1422: Loop Design: NMN Binder
Status: Closed


Name: 1422: Loop Design: NMN Binder
Status: Closed
Created: 08/25/2017
Points: 100
Expired: 09/01/2017 - 23:00
Difficulty: Intermediate
Description: Redesign the loops of this protein to better bind the ligand! Nicotinamide mononucleotide (NMN) is a small-molecule that makes up part of the small-molecule nicotinamide adenine dinucleotide (NAD), which is sometimes regarded as 'the molecule of youth.' Scientists know that the amount of NAD in our cells declines as we age, and so designing a protein to bind to NMN is the first step towards achieving protein-based biosensors that can detect NMN levels in cells. Such biosensors would help scientists to understand the aging process and could potentially lead to a 'cure' for aging!

The starting structure of this puzzle is a protein designed to bind NMN, but we think it can be improved. There are several loops near the NMN binding pocket that could be extended to make stronger interactions with the ligand. In the selected loops, players may insert and design up to 10 extra residues for free; additional residues may be added at a cost of 20 points per residue. Most of the protein backbone is frozen, and there are strong constraints to keep the ligand positioned in the binding pocket. There are permanent cutpoints flanking each loop, so that players may freely manipulate the loops without disturbing the rest of the structure.
Categories: Design, Overall

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Joined: 05/18/2012
Groups: Contenders
I think the permanent cuts are a hindrance and nuisance

Not so much the cuts on loops, somewhat on the helices, and extremely on the sheets. I depend heavily on visual alignment of sheets and the permanent cuts mean that I have no idea how well the resulting strands align. I haven't tried working with the cut helices portions yet, but am pretty sure it will be nearly as annoying as well.

I would prefer to control the rest of the structure by my terms and not have everything look permanently "broken".

It would be helpful to know how other players feel about this.

Joined: 05/18/2012
Groups: Contenders
Changed to loops

Probably best to just ignore the post. I changed the cut points to loops and just ignore them. I don't suppose it'll make much difference in the long run.

Also, an editor can remove the duplicate comment. There were transient server issues when I initially tried to save it.

Joined: 06/24/2008
Groups: Void Crushers

In fact I crash whenever I try using any Ligand tools.
Have we ever gotten an explanation how to use those tools? There is no tutorial on them.
I have now crashed running two different mutate scripts on 1422. Though I have mutated in rebuild and BIS scripts.

bkoep's picture
User offline. Last seen 13 hours 9 min ago. Offline
Joined: 11/15/2012
Groups: Foldit Staff
Avoid ligand tools!

Apologies! The ligand tools should not even be available in this puzzle—there must have been an error in the puzzle setup. As Susume speculated below, the ligand is to supposed to remain unmodified in this puzzle. We are only interested in changes to the binding protein.

Susume's picture
User offline. Last seen 3 hours 56 min ago. Offline
Joined: 10/02/2011
Ligand tools?

Are the ligand tools supposed to be enabled in this puzzle? I thought the ligand was supposed to stay the same, not let us edit it. And yes, the ligand tools crash the game - I suggest not using them.

Susume's picture
User offline. Last seen 3 hours 56 min ago. Offline
Joined: 10/02/2011
Seeing bonds to ligand

You can turn on Show bonds (non-protein) in the View menu to see bonds to the ligand. Turn on any of the color schemes that include "CPK" to see the bondable atoms (the red and blue ones). If you don't see these options in your View menu, click Menu, Options, Advanced GUI.

Susume's picture
User offline. Last seen 3 hours 56 min ago. Offline
Joined: 10/02/2011
Marcos design?

Was this protein designed by Enrique Marcos? It looks a lot like 5L33 in the PDB.

bkoep's picture
User offline. Last seen 13 hours 9 min ago. Offline
Joined: 11/15/2012
Groups: Foldit Staff
Good eye!

Yes, the initial design was derived from one of Marcos' de novo-designed NTF2 folds.

toshiue's picture
User offline. Last seen 4 days 22 hours ago. Offline
Joined: 01/31/2016
Groups: Go Science

All three current puzzles (1420, 1421, 1422) are reporting higher scores on the clients (for my group) than the site's reporting. Worst of the three is 1422 which shows me at 5th on the client but 11th on the site. Other group members reporting the same.

LociOiling's picture
User offline. Last seen 8 hours 37 min ago. Offline
Joined: 12/27/2012
Groups: Beta Folders
scoreboards not updating

I just added a forum post on this issue:


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