puzzle picture
529: CO2 and You!
Status: Closed

Summary

Name: 529: CO2 and You!
Status: Closed
Created: 03/14/2012
Points: 100
Expired: 03/21/2012 - 23:59
Difficulty: Advanced
Description: Help fix this novel carbon-fixing enzyme. Try varying loop length and structures to make better scoring interactions with the ligand. In this puzzle, the first of a series, up to 7 residues can be added, and up to 10 can be removed. If you are new to Foldit, make sure you have completed Intro Puzzle 5-2, 7-1 through 7-4, 8-1 & 8-2 before trying this Advanced Science Puzzle. More info in the puzzle comments.
Categories: Design, Overall

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Comments

beta_helix's picture
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Here is some background information on this puzzle:

https://depts.washington.edu/mllab/files/CO2ProjectWebsite.pdf

With many other questions answered in the Scientist Chat with CEiben: http://fold.it/portal/node/992115

As mentioned in the chat, please post any questions for CEiben about this Puzzle here!

brow42's picture
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Joined: 09/19/2011
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Wiggle Lock

Just a heads up, I think segments 33, 60, 61, 119, 169, 248, 380, and 410 are what rav3n calls 'wiggle locked'. Bands to these are ignored.

CEiben's picture
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@thom001 Designing new loops

@thom001
Designing new loops and interactions for ligand 420 (C1) is preferred over 419 (B1). It's not clear a priori what kinds of interactions will help so I recommend being creative.

@brow42
I'm having trouble reproducing the 'wiggle lock'. When I wiggle after banding between 33 and 60, the residues move together on my computer. More information on how to reproduce this lock would be very helpful since it's not intentional in this puzzle.

brow42's picture
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Wiggle Lock

I test these by making a strength 10 band between the segment and a locked segment, such as 1. I then do wiggle for 1 iteration, and check the change in score. Then I quickload for the next segment. The listed segments all show a change in score identical the unbanded case.

In the latest flu design puzzle, all the wiggle locked segments had constraints, but not all of the segments with constraints were locked. That was the first time I used this method.

I modified http://fold.it/portal/recipe/39029 for the new puzzle, but didn't upload it because my main client is doing other stuff. I can probably upload a new version in the morning.

beta_helix's picture
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Joined: 05/09/2008
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We think we might have found the cause of the "wiggle lock"

so hopefully it'll be fixed in the new Flu Puzzle that will be posted next week.

Thanks for your patience with this one.

Joined: 08/24/2011
Groups: Go Science
It's possible to make a

It's possible to make a rebuilding script that works on specified non-consecutive portions of the protein. You just need to talk Rav into making the necessary modifications to DRW (assuming it's not already in the options somewhere; I haven't looked.)

Joined: 08/24/2011
Groups: Go Science
(Above comment intended to

(Above comment intended to reply to mott, below.)

Joined: 08/30/2011
numbering

is a consecutive numbering of the editable segments possible?
as it is right now, it is impossible to run a rebuilding script or at least it is not possible to run my top fav: DRW.

beta_helix's picture
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I'm sorry

but sadly there is no way for us to do this, Rosetta needs the entire chain to be numbered consecutively.
You'll need to work on rebuilding the loops individually when using that script instead of all of them at the same time.

Joined: 08/24/2011
Groups: Go Science
Positioning

Question based on my total ignorance of dynamics at this scale: is there any reason to worry about how the ligands move into place? They seem to be in the center of the protein, so I don't see an obvious path in or out. Is it possible for us to change the backbone in such a way that the ligands are nicely bonded into place, but there's no way for them to actually reach that position or leave it?

CEiben's picture
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@mbinfield

Good question. Ligand 419 (B1) is actually a cofactor which aids in catalysis, and doesn't leave the enzyme (meaning it can be very buried since it only needs to find its way in once). Ligand 420 (C1) is the substrate which needs to get in and out of the enzyme. Enzymes are known to breath and be flexible, so there is some leeway, but it is theoretically possible to build a loop that would close off the active site completely. On the other hand, there are natural enzymes that have "caps" which close off the active site during catalysis before opening it back up to solvent. Basically it's safer to leave a space for the 420 (C1) to get in/out, but its theoretically possible to design a cap which is meant to open and close (though I don't know of any rationally designed examples off hand).

Joined: 02/11/2012
Groups: Geekdo
CO2

Does the CO2 adhere to the surface of the ligands for conversion, or how is the actual chemistry envisioned?
Adsoption, migration, conversion, or first anexchange of electrons in the vicinity of the protein, followed by dissolution of the CO2 molecule and reconfiguration?

CEiben's picture
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This enzyme catalyzes a

This enzyme catalyzes a critical step in a new CO2 fixation pathway in which 1 carbon molecules are built up into larger molecules that work with native metabolism. So this enzyme doesn't work with CO2 directly and is only one step in a pathway.

Joined: 12/07/2011
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add remove residue

How do we add or remove residues?
Beta Helix said we can add 7 and remove up to 10.
I see only the mutate tool. We can only change but not add or remove.

spvincent's picture
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You need to be in design mode

You need to be in design mode (press 4) and ctrl-click on the residue where you want to add/delete.

beta_helix's picture
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I forgot to mention that in the puzzle comments

Sorry, I have added these instructions:

If you are new to Foldit, make sure you have completed Intro Puzzle 5-2, 7-1 through 7-4, 8-1 & 8-2

Joined: 12/07/2011
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Oh....Thanks spvincent and

Oh....Thanks spvincent and Beta Helix!

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