How To Study Protein Structure Evolution

Question

[bharat.85.monu]

HI,

I have created a data-set f non-homologous protein sequences from PDB in order to study certain secondary structures. After that, I obtained a list of homologues for those non-homologous protein structures to evaluate what happens to that sec-str in homologues. Now, I am looking for a reference how to move forward with this approach and study the evolutionary conservation of that sec-structure ... Can anybody guide me in this regard ??

Thanks

BHARAT

Answer 1

[Charles Warden]

I think your study design sounds a little confusing (for example, how did you find homologs to a set of non-homologous proteins?), but I would recommend starting with a Google Scholar search for "protein secondary structure evolution".

I'm somewhat familiar with studies on protein evolution (though mutation rates in non-synonymous sites), but I don't recall any specifically focusing on secondary structure. Here are a few examples I knew off the top of my head (where you can use the citations to search for other related studies):

http://mbe.oxfordjournals.org/content/25/4/634.short

http://rd.springer.com/article/10.1007/s10709-006-9125-2

[bharat.85.monu]

For each non-homolog, I searched for homologues using BLAST. Do think this kind of approach is wrong ??

[Charles Warden]

I mean, I think it depends upon your goals - I guess this means there are no paralogs in your species of interest and you want to see if there are homologs for that unique gene in other species?

I'm not really an expert on protein modeling, so I probably can't provide a lot of specific advice.

[5heikki]

Keep in mind that BLAST is a Basic Local Alignment Search Tool so your hits can easily represent totally unrelated proteins that happen to share some domain with your query sequence. I think in silico protein structure prediction is still largely pure speculation (same goes for RNA structure), but I'm in no way an expert or even an advanced beginner in this field. A while back I read some fascinating articles about protein folds in the context of viruses (e.g. here) but I'm not so sure it's really relevant for your stuff.

edit. meant as a reply to bharat's comment