| abstract
| - The alignment tool lets you copy and paste the 3D structure of known proteins onto your protein in a puzzle. This is useful, because we know that evolutionarily related proteins have similar structures, and being able to copy the structure of known proteins gives us a huge headstart in folding their relatives. We start by copying the location of the backbone atoms from the known protein into the puzzle's protein. For indentical sequences, this is easy! - we just copy the first residue of the query from the first residue of the template, the second from the second, and so on until we're done. But we're not dealing with identical proteins - we're dealing with related proteins. Through evolution, a protein will change some of its amino acids, or delete some, and possibly insert some others. So what happens when the sequences have different amino acids? Or what if they have different lengths? There wont always be a lucine to match to a lucine, or a lycine for a lycine. Here's where we need the idea of an Alignment. An alignment is a sort of chart where you can look up a residue in the query template, and it will tell you which residue in the template you should copy the coordinates from. In the alignment tool, the top row are the residues from our current puzzle's protein, and the letters beneath them are the residues which they will copy from. A lot of residues will be copied from letters that dont match - this is ok. Just because the letters dont match doesn't mean that copying the coordinates is bad. But getting a letter match is a good thing. A color match is also good, but not quite as good as a letter match. Sometimes in order to make the letters match up better, an alignment will have a gap, where there's no corresponding residue. Gaps are inserted to make the other letters and colors line up better. They are also necessary because it's rare that even related proteins will have the same length, so you'll have to have gaps somewhere. Usually, you'll start a puzzle with an alignment that the computer generates for you. This alignment just tries to maximize the letter and color matching. It is, in a sense, very dumb. It is dumb because it ignores the 3D structural consequences of the alignment. You can match all the residues you want, but if the resulting structure doesn't work, then that alignment didn't work. This is where humans come in. The alignment tool lets you adjust the computer generated alignment so that it makes sense structurally. The player's task is to figure out which regions of the alignment should be kept, and which parts need to be adjusted. Usually this means identifying which regions are the most crucial to the proteins structure (usually the interior, hydrophobic core), and trying to match better on those regions, while sacrificing matches in the tails or exterior loops. Then the player must figure out how to resolve these exterior regions that dont match using the standard tools of Foldit! Note: Cutpoints were introduced April 2012 - they are explained in the tutorials - if you are having trouble seeing them switch to line in the view menu temporarily - they show up very well. Alignment Panel - tool update 18 July 2012* The alignment panel now has a 'score' in the title bar. This score gives you an estimate of how good your structure is. Think of it as how well your fold will do if you resolve the cutpoints and shake the structure out.* The alignment behavior has been changed slightly. Now you can single click the align button to simply align once, and you can double click to lock to the alignment, like before. Clicking again while locked will unlock it.* The old 'score' has been renamed 'match', as it gave the false impression that players should attempt to optimize this number (the new 'score' should be much better for this purpose).* The alignment intro levels have been updated to reflect these changes
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