Bo Yang wrote: > I have a question of modelling the C-terminal region of my target. The > protein matches with the crystal structure templates except the > C-terminal region (named as C-tail here). I did BLAST search using this > segment to against the proteins with known structures at Protein Data > Band. It returns a match with a short region of an antibody at 56% > sequence identity with the inclusion of 4 gaps. The function of my > target protein has nothing to do with antibody. I am not sure if it is > reasonable to use the BLAST match results as templates to model the > conformation of the C-tail. > > I have thought to model this C-tail region using the “Loop Model” in > Modeller. There are some concerns here. First, the C-tail contains 24 > amino acids. Will this be too long for the loop-model in Modeller? If > the length is not the problem, how reliable are the conformations of the > segment? Second, the segment is at the C-terminal of the protein. For my > understanding, the “Loop Model” in Modeller requires the N’ and C’ > terminus of the segment to be fixed. The position of the last residues > of the segment will have significant influence on the “Loop” > conformation. Which one is more reasonable, to model this segment based > on the sequence homology, or use a loop modelling algorithm?

You will have a lot of trouble modeling this with the loop modeling procedure. 24 residues is far too long, even for a loop with both ends fixed (15 is about the limit). With a non-fixed C terminus, the space to sample is just too large - the loop will be free to explore too much space. If you have some other information about the loop (e.g. interactions with other protein residues or ligands) then that might help to reduce the search space. Otherwise, it is probably best to remove these C terminal residues from your model.

Ben Webb, Modeller Caretaker