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Recipe: Bridge Wiggle v 1.2.1 - Brow42
Created by brow42 82 428
4.441175
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Name: Bridge Wiggle v 1.2.1 - Brow42
ID: 37416
Created on: Fri, 01/13/2012 - 16:09
Updated on: Wed, 10/30/2013 - 01:18
Description:

Randomly wiggle cysteines with bands to improve bridge score. Also band them to form the bridges in the first palce. Auto detects close pairs.



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brow42's picture
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Joined: 09/19/2011
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Optimize the disulfide score

This uses bands-to-space to randomly move the ends of your cysteines around, keeping any improvements in the total disulfide score. This is a random-walk hill-climbing algorithm. The last 2 atoms in each cysteine are randomly banded to space and if the total disulfide score increases, the configuration is saved.

Bands will have random strengths and lengths up to the values you specify. You can also include an unbanded wiggle periodically. Bridge wiggle runs until canceled. You can get the best disulfide scoring configuration from quicksave #3, and the recent best is available the usual way.

Defaults are for CASP Roll 3. This recipe will remove bands. This script will run forever, check the output window to view the progress.

Click 'More' to initially band the cysteines. This bands the SS bond to 2.05, the C-S between cysteines to 2.73 and C-C between cysteines to 3.26 (based on CS bond being 1.8). This arrangement should pull the CS bonds to be 90 degrees to the SS bond, and the two CS bonds also at right angles to each other. This seems to score higher.

brow42's picture
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Joined: 09/19/2011
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Update 1.0.1

The script now find all the S-S distances and pairs them up, closest pair first, then second, then third. Any pair closer than 3.5 is considered a possible bridge and added to the initial defaults. 3.5 is an arbitrary number, but the bigger the cut off, the more the protein will be distorted if band up the pairs to try to make bonds.

The algorithm isn't perfect, if 4 Cys are clumped together, they can pair 3 different ways. It will pick the one with shortest distance.

brow42's picture
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Joined: 09/19/2011
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Update 1.1

* Version 1.1.0 June 16 2012 Brow42
* Now handles first/last cysteine in protein properly
* Removes wiggle bands on cancel
* New option boxes: band S-S together, wiggle backbone atom, use sidechain score
* Fixed incorrect random band (only did hemispheres)
* Auto-selection of possible bridges expanded to 4.0 A

brow42's picture
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Joined: 09/19/2011
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Update 1.2

Sorry there hasn't been any updates...I meant to do a substantial rewrite of this recipe...but never finished it.

Here is two requested features...1) User bands are preserved! Requested many times. Sorry for not putting it in. 2) Adjacent cysteines are not auto-selected for pairing. This occurs in nature, but rarely. If you WANT to pair them, you can edit the pair list at the top of the dialog. Copy/Paste is allowed, which can save you some typing.

Joined: 04/25/2013
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This pretty darn sweet...

I'm still getting the hang of FoldIt and this is the first recipe I downloaded so it is theoretically possible I'm too excited over something that old hands will think was "just a normal FoldIt recipe", but this was really gratifying so I wanted to leave a note as a breadcrumb for anyone else in a similar position in the future.

So the first question to answer for newbies is "What is this recipe even for?" The answer is that there are amino acids (the cysteines) that have sulfur atoms in them (not particularly visible in the standard FoldIt rendering). In real chemistry special bonds can form between two sulfers. If you have the ability to see "bonds" turned on, the blue ones are normal hydrogen bonds, but between two cysteine residues you can get a GREEN bond, which looks like the pictures in the fold it wiki article on disulfide bridges.

If you just rubber band two cysteines you want to form a bond like and then just wiggle naively for a while this there is a good chance NO GREEN BOND will form. That's where this recipe comes in. This recipe, once it knows which cysteines you want next to each other, will "magically" use rubber bands and wiggling, over and over with undo-ing, to make a green bond form with a reasonably good total score.

So the thing you need to do are dowload this recipe, and then learn out to tell the recipe what cysteines to put next to each other. For reference, Brow42 was in the global chat when I asked about whether disulfide bonds were even POSSIBLE and he was there whenever I had issues. My goal with this comment is to let you repeat my success without having to have Brow42 there to hold your hand the way he helped me.

To download the recipe I was already logged in on the client, but I had to also be logged in on the website. To do this I opened a "log in to comment" link in a new tab, and then reloaded this page and then there was a green "Add To Cookbook!" button.

Once you've downloaded the recipe, you run it by clicking on the recipe in your cookbook menu. It will pop up a dialogue with a bunch of options. Don't panic. In the text box you need to enter at least one pair of comma separated numbers, like "20,40" or whatever. How do you get your numbers? There are two basic ways:

If you want to be all clever and human about it, and you know exactly which bits of your protein you want next to each other with a green bond between them, put your mouse over each bit and hit the button on your keyboard. It will pop up an informative window that includes the NUMBER of that amino acid for use by the recipe. In order to do this you'll need to know which amino acids are cysteines in the first place so that you even know what to point your tab button at... Look for the unbranched "two segment long" orange residues. Those are the cysteines!

If you want to move fast and not bother with eyeballing things, the recipe has a super cool feature: if you open up "show output" (even before it makes any changes) you'll see a printed report telling you the number of EVERY CYSTEINE THERE IS, including suggestions about which ones would be easy to pair based on their current proximity. So for reasonably small proteins, you could theoretically just try every possible cysteine pairing with a protein between each pair attempt, and jot a not to keep the one that "looks best".

BUT WAIT THERE'S MORE!

In addition to all these abilities, you can give the recipe MORE THAN ONE CYSTEINE PAIR and it will try to put each pair in contact simultaneously. So if all of these numbers were cysteines in a protein you could give the dialogue box "11,28 20,40" and let the recipe run, and (if the folding is feasible) end up with TWO green bonds in your structure.

Anyway, this was the first real "magic spell" I learned as a FoldIt newbie, and when everything just fell into place it really did kinda seem like magic. Five stars to the recipe, and thank you to Brow42 for the work and the help in the chatroom :)

rezaefar's picture
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Joined: 07/08/2014
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Thanks Jennifer

You explained very well.
Thank you.

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Developed by: UW Center for Game Science, UW Institute for Protein Design, Northeastern University, Vanderbilt University Meiler Lab, UC Davis
Supported by: DARPA, NSF, NIH, HHMI, Amazon, Microsoft, Adobe, RosettaCommons