Fragment Filter and the Remix Tool
Foldit designs have come quite a long way, but there are several issues that we're still seeing in player-generated models.
One of the biggest problems is that some regions (primarily loops) in your models don't match the shape of regions in known natives. Since some shapes are more common than others, this means that these shapes are less statistically likely, and have a reduced probability to fold up in practice.
With that in mind, we've created...
The Fragment Filter!
So first - What is a fragment? A fragment is a shape for a small region of the protein. Imagine a loop of 8 residues. Loops can have drastically different shapes, and each of these shapes is a fragment of size 8.
The Fragment Filter tells you when part of your protein has an unrealistic fragment.
It does this by marching through the protein, looking at every fragment of size 4 (overlapping). For each of these fragments, it does a look-up into a database of known fragments that have been generated from a set of natives. If it cant find any fragments with shapes similar to the one you have in your protein, you'll get a score penalty, and it will highlight the fragment as a bad fragment.
The bad fragment is shown by the glowing red residues.
In this way, we ensure that the models you are generating are composed of statistically likely fragments, increasing the probability that they will fold up in the lab (and therefore the probability that we will test your design!).
From our analysis, top Foldit design solutions usually have 1-3 of these bad fragments.
So if your design has a bad fragment... how do you fix it?
The Remix Tool
Remix changes the shape of the selected region to match a 'good' fragment.
There are a couple of basic steps to using the Remix tool:
1. Select the region to remix.
Remix will work on selections of size 4-10. Even if there are only 4 bad residues, you can try larger sizes to try to get better results out of Remix. Just make sure the bad fragment is included in the Remixed region.
Here we've selected the bad fragment. In the Classic interface, Remix will work on secondary structure.
The Remix button will pop up when you select regions of size 4-10.
2. Remix the region!
When you hit Remix, the tool will do a lookup into a database and find a shape that has the same size and similar endpoints. Then it copies this shape onto your protein.
Remix wont always find something to copy (though it usually does), so you might have try selecting a different region, or modify the one you have until it finds something.
By using Remix, we've fixed the bad fragment, but this has created issues in the rest of the protein.
3. Resolve the resulting issues.
Similar to the Idealize tool, using Remix will create global changes even though you're just modifying a local area. This can cause issues elsewhere in the protein that you'll have to fix.
One way to fix them is to use low clashing importance and bands to stabilize the structure.
Another option (my favorite) is to insert a cut near one end of the region before Remixing, and then wiggle that region after Remixing until the cut can be closed. This prevents the global changes from ever happening, and usually works pretty well!
By using other game tools, we can bring the structure closer to its original shape, without the bad fragment.
Remember that you can fix the bad fragments any way that you want - Remix might just make it easier. It will be available on any puzzle that uses the Fragment Filter.
Like always, we'd love any feedback that you have on both the Fragment Filter and the Remix tool.( Posted by jflat06 76 709 | Wed, 11/13/2013 - 22:02 | 5 comments )