I am not sure if this is the correct forum to ask this question, but I thought many people here would have knowlege to answer me.
So Rosetta designs proteins using normal amino acids such as Methionine (MET), but most proteins are then taken to bacterial system for expression (rather than mammalan/insect expression systems), bacterial systems which use N-Formylmethionine (fMET) as its initiation codon. Some bacterial species would also use Selenomethionine (MSE) instead of Methionine throughout a protein.
Maybe this is a very basic question, but won't these different methionines impact the final structure of the protein? Should I put this issue under considiration when designing proteins? expecially if they were imbedded in the core? Can someone explain to me the general picture, or point me to a resource that explains this?
I hope my question is not too NEWB to be answered.
Selenomethionine is biologically very similar to regular methionine. I am unaware of it being used in biological systems; it's used in crystallography because the heavy SE atoms can be identified, making phasing easier. Because of its use in crystallography, a lot of the "methionine" used to make the databases used to make the scorefunction may have been selenomethionine anyway (I am unsure that the condition is filtered for when making training sets), so it's likely that the scorefunction is tuned for both seleno and regular methionine anyway.
An N-terminal modified methionine is unlikely to be buried in the core of the protein because of the N-terminus: burying that charge is hard. I agree that if you have a chemically modified terminus - we are talking extra atoms here? - that modeling the atoms will be important, especially if the terminus is buried. For most systems, the N-terminus ends up being flexible, or irrelevant, or the system has an N-terminal expression tag anyway, or ...... you get the idea. There are going to be edge cases where an fMET is critical to conformation - but you should be able to identify those from the N-terminus generally being important, and then know not to trust a model that uses the wrong N-terminal atoms.