Hi all, I have a very basic question: In case of homology modeling, is it preferable to model one domain at a time or the entire structure at once? In other words, when I use a template prediction tool, should I give a query, say 3 times for a 3-domain protein or one query for the entire protein? If the answer is domain wise, then how should the assembly of the entire protein be made, especially in case where multiple templates are used
I guess it all depends...Do you have a homologous protein for which the structure off all three domains has been solved? If you do, you can probably use that to model your protein. If you do not have such a structure, I would do homology modeling on three separate domains. How to reassemble them into one protein is another question. Without good structural information from an homologous protein, I would not try to reassemble these three domains into a single protein. I would try to use the three separate domains to learn as much as I could and hope that someone will solve the real structure soon. I think Rosetta has made some claims about trying to reassemble these domains, but I do not know how well that approach works...
I did as Dan and Whetting have said--modeled the host domains individually on the yeast full length template --and it's making sense to me, so thanks to both! The sequence similarity of all domains is just about 26% for all but structurally, they seem to be okay to start with. However, I'm having problems with superimposing all three domains at once on the template. Although this is possible with the tool I'm using--Discovery Studio 3.5 (standalone) I'm not able to save the superposed file in the .pdb format. Is there an online server to do this (or better still, fix this problem on DS itself)? Pymol installation is right now on hold because of a local server interference, so I'd like an online alternative to do my job until Pymol is up and running again.
Guess I'll keep coming back here until my model is all ready!