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680: Solo Hand-Folding Sepsis Puzzle
Status: Closed

Summary

Name: 680: Solo Hand-Folding Sepsis Puzzle
Status: Closed
Created: 02/26/2013
Points: 100
Difficulty: Intermediate
Description: Sugar molecules such as the one here are coated on the surface of many human pathogens. We are attempting to increase the protein-sugar binding interactions by allowing you to redesign & insert up to 10 residues to form additional hydrogen bonds with the sugar. To encourage this, only GUI scripts are allowed, and sharing has been disabled. After this puzzle expires, the puzzle will be re-posted and LUA scripts and sharing will be allowed. You will be able to load in your solutions from the first puzzle and refine them with scripting and sharing. Please read the new blogpost & puzzle comments for more details.
Categories: Design, Hand-Folding, Overall

Top Groups

RankGroupScorePoints
1Anthropic Dreams9,946100
2Go Science9,90087
3Another Hour Another Point9,55075
4Contenders9,43164
5Team Schleswig-Holstein9,39855

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Comments

Joined: 05/09/2008
Groups: None
Additional info about this puzzle:

Please read the new Blog Entry about this puzzle: http://fold.it/portal/node/994592
___________________________________________

We realize that not everyone loves Hand-Folding puzzles, but don't worry:
the "normal" version of this puzzle will be reposted next week (allowing you to you to load in your manual saves from this puzzle).

The motivation for making the initial round of this Sepsis Design Puzzle "Hand-Folding only" is because the goal is this puzzle is to increase the number and strength of protein-sugar interactions. This is very hard to do with scripts, so we'd really like you to focus on trying to do that manually.

We have unlocked GUI scripts, not because we want you to heavily use & rely on them, but so that simple things like shaking/wiggling don't have to be manually done all the time.

Sharing has also been disabled for this round, as we want to try to get as many diverse solutions as possible before players start evolving their teammate's solutions.

We know this puzzle will require a larger time investment than usual (which is why it is up for over 10 days) but hopefully the goal of this puzzle will make that time investment worthwhile.

___________________________________________

If you are new to Foldit, make sure you have completed Intro Puzzles 7-1 through 7-4 before trying this puzzle.
___________________________________________

This puzzle has the ResidueIE filter on (to ensure PHE, TYR, and TRP residues are scoring properly) and we've increased the Ligand Score by a factor of 10 to promote interactions with the sugar.

Tip: To see the parts of the sugar that you can bond to, check Show bonds (non-protein) and Show bondable atoms in the View menu. Make sure Show bonds (loop) and Show bonds (sidechain) are also on. Blue can bond to red, and purple can bond to either blue or red.
___________________________________________

Crash Warning: Do not enable the 'Show Isosurface' view option, as it will crash with this puzzle. We hope to fix this soon!

Joined: 06/04/2012
scoring well or not scoring well

I get a penalty using TYR so I assume the above text regarding the residue filters should be NOT scoring well when using PHE, TYR and TRP or the filter is wrongly applied

Joined: 05/09/2008
Groups: None
Sorry for the confusion, hansvandenhof

I have reworded this sentence so that it reads "to ensure PHE, TYR, and TRP residues are scoring properly".

The main purpose of the residueIE filter is to prevent unrealistic residue substitutions in Foldit.
For example, it makes adding tryptophans, tyrosines, and phenylalanines on the surface of a protein score poorly. Putting hydrophobic residues on the surface is bad because it makes the protein very "sticky", likely to interact with many other proteins, including itself, and hence not very useful.

So when I said we want them to score "well", I meant that they should only get a high Foldit score if they are in the proper location in the protein (most likely buried in the core of the protein), as we want your designs to be as useful as possible, since the problem we are trying to solve with this protein is already hard enough!

Joined: 06/04/2012
Hi Beta, thanks for the quick

Hi Beta, thanks for the quick response.

But still i'm wondering whether it works like you wrote. When I have a PHE buried deep in the protein near the ligand and no exposed is showing I assume it should not be penalized by the filter then. But still it does, so.....! Or is it maybe that there are very specific places where it scores well? but that would be strange because then you apparently know where they should come. Puzzling:-)

Joined: 06/24/2008
Groups: Void Crushers
Closing the cuts

I assume the cuts are unclosable, yes? or maybe I just havent figured out the right distance.

Joined: 05/09/2008
Groups: None
Correct, the cuts cannot be closed

They are just there to hold the region you are able to work on in place, without moving the rest of the frozen protein when you wiggle.

Joined: 06/04/2012
Filtering

Hi Beta,

I think you haven't seen my question about the placement of PHE, TYR and TRP in relation to the filter^^

""Hi Beta, thanks for the quick response.

But still i'm wondering whether it works like you wrote. When I have a PHE buried deep in the protein near the ligand and no exposed is showing I assume it should not be penalized by the filter then. But still it does, so.....! Or is it maybe that there are very specific places where it scores well? but that would be strange because then you apparently know where they should come. Puzzling:-)""

tamirh's picture
User offline. Last seen 1 year 19 weeks ago. Offline
Joined: 05/11/2012
Hi hansvandenhof, Could you

Hi hansvandenhof,

Could you do a couple things to help us figure out exactly what's going on here?

1) Save your solution and tell us the name of the save
2) If you are using devprev, press TAB on the residue in question and scroll down past all of the energy values. You should see "ResidueIE Filter:" and then a line giving you the "Interaction Energy" and "Required". Tell us what those values are. If you are not using devprev, the change that adds this data should be going out to main later today

Thanks, and hopefully we can get this figured out.

Joined: 06/04/2012
Filtering

Hi tamirh,

I recreated the situation and saved in as: "filter issue" Obviously this isn't my best fold but made especially on request.

Interaction Energy: -0.560824
Required: -7.5

The TYR is hidden well, no exposeds but still the filter pealizes.

Thanks for your help

regards
Hans

tamirh's picture
User offline. Last seen 1 year 19 weeks ago. Offline
Joined: 05/11/2012
Ligand Issue

I pulled out the ligand to find out if the ligand would cause the IE to change. It does, but only negatively. With the ligand completely removed, the IE is basically the same as when it is there.

I then replaced the ligand with some ALA to test out if it was a difference between ligands and normal aa. The buried TYR still scored poorly. So it looks like it's just a function of the interaction energy and positioning itself, not an issue with it being a ligand.

Susume's picture
User offline. Last seen 6 hours 59 sec ago. Offline
Joined: 10/02/2011
Tip for new folders

Tip: To see the parts of the sugar that you can bond to, check Show bonds (non-protein) and Show bondable atoms in the View menu. Make sure Show bonds (loop) and Show bonds (sidechain) are also on. Blue can bond to red, and purple can bond to either blue or red.

Joined: 05/09/2008
Groups: None
thanks

Thank you Susume, I added this to the first comment as well!

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