I'm very much a beginner at modeling, and this question might be very trivial. I hope you still would hint me about the answer, for it would help me a lot.
I have a large protein (say 1500 residues, let's call it protein A) and its homologue (protein B) of about the same size. Both proteins have published crystal structures.
Both proteins have a key structural element, loop L. The loop is poorly resolved in structure A, but well resolved in homologous structure B.
Now, I can take just the L loop regions as separate PDB files from both A and B and do homology modeling of A based on B; this works really well. But I also would like the model to consider the surroundings (the rest of the structure) when evaluating the energies.
Thus, I'd like to keep the REST of A's crystal structure intact, and only model loop L based on the structure of the same region in protein B.
How can I achieve that?
Thank you in advance!
- Alex Predeus Michigan State University
On 10/31/2011 12:02 PM, Alexander Predeus wrote: ... > Thus, I'd like to keep the REST of A's crystal structure intact, and > only model loop L based on the structure of the same region in protein B.
It sounds like you don't really want to do "loop modeling" in the Modeller sense here (that is designed for loops where you don't know have a template structure). So really what you want to do is build a model using template A for the non-L regions, and template B for the L region. That's basically FAQ #1: http://salilab.org/modeller/9.10/FAQ.html#1
You will also want to include a little bit of the neighborhood of the L region from B, so that A and B overlap in this region. Otherwise, the loop will be poorly oriented relative to the rest of the protein.
This will build a model that resembles the A backbone, but most likely the sidechains will move. If you don't want to change the original A structure at all, select only the L region for refinement: http://salilab.org/modeller/9.10/manual/node23.html
Ben Webb, Modeller Caretaker