Analysis of protein folds and alignment of secondary structure elements

If you have predicted that your protein will adopt a particular fold within the database, then an important thing to consider to which fold your protein belongs, and other proteins that adopt a similar fold. To find out, look at one of the following databases:

(Note that these databases don't always agree as to what constitutes a similar fold, so I would recommend looking at as many of them as possible).

If your predicted fold has many "relatives", then have a look at what they are. Ask:

Core secondary structure elements, such as those comprising a beta-barrel, should really be present in a fold. If your predicted secondary structures can't be made to match up with what you think is the core of the protein fold, then your prediction of fold may be wrong (but be careful, since your secondary structure prediction may contain errors). You can also use your prediction together with the core secondary structure elements to derive an alignment of of predicted and observed secondary structures.

For example, we predicted that the glutamyl tRNA reductases (hemA family) would adopt an alpha-beta barrel fold using a combination of fold recognition and secondary structure prediction methods. We aligned the secondary structures of diverse members of the alpha-beta barrel fold using a structural alignment program, and aligned the secondary structures to the core (boxed below) secondary structure elements.

In the alignment above, each alpha and beta character refers to an entire secondary structure element. Those that are boxed are core secondary structure elements found in most members of the fold. The alignment of predicted secondary structures to the core elements appears at the bottom of the figure. Note that I have had to delete several alpha helices and beta strands from our prediction to allow for alignment. This is not surprising, because insertions or deletions of secondary structure elements are common across the diverse set of proteins that adopt this fold.

Next sequence to structure alignment.

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