88% is a lot

Thanks to the fantastic blog In the Pipeline I found this article in PNAS about proteins with 88% sequence similarity having vastly different folds. (Apparently, it had been incredible to conceive of a protein with 50% sequence similarity having such a vastly different fold not too many years ago, this review article also in PNAS provided some handy context). Anyway, I'm thinking about writing a term paper for my topics in biochemistry class about this. At first I was thinking it would be about the limitations of just looking at sequence similarity for homology (as I did many many times with BLAST aligns in genetics class), but there seems to be much more powerful concepts to get at here. Because even something vastly different in function can be evolutionarily related. Basically these studies of testing the number of residues that can be changed (either to create drastic changes in folding or to see what the limit in number of residue mutations to retain native folding is) and studying where the mutations must occur is a studying the evolution of different folds of proteins. There could be one fold that is evolutionarily related to another fold via some residue that is mutated whose net result is to switch a helix to a sheet or what have you via how it can make favorable contacts. You could even potentially map out "phylogenies" of sorts of different protein folds to see how they are related to one another. Well, kinda.

Now let's see if I can pull this together to make an awesome term paper instead of a bunch of scattered ideas.