Hi Graham,

It is not clear to me what exactly your situation is. Do you want to use the "loop templates" only for the loops and discard the rest of the structure? Or do you want to use those template also for the rest of the structure but you would like to give a higher weight to the template without the loops?

In the first case you could do what is suggested in FAQ #5 as you mentioned. You are right that this might be cumbersome in your case. An alternative is to treat each loop as a separate template. Let's say template X has two loops that will be used; residues 10-15 and 25-30. If Y is the "loop-less" template the alignment (PIR format) would look something like this:

P1;X1 structure:X:10::15::::: ---------XXXXX------------------------------------------------------* P1;X2 structure:X:25::30::::: ------------------------XXXXX---------------------------------------* P1;Y structure:Y:1::50::::: YYYYYYYYY-----YYYYYYYYYY-----YYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYY* P1;target sequence:target:::::::: TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT*

In this case it is important that there is some overlap between the loop region of X (X1 and X2) and the template Y in the alignment. The anchor residues of the loops should be aligned with the corresponding residues in Y to make sure MODELLER gets the relative orientation of the loops correctly.

The second case is simpler. If you can use the full structure of the loop templates (i.e. the loop templates are homologues of the target sequence) but you want the "loop-less" template to have a bigger weight you can simply add more copies of this template to the alignment. It would be like this:

P1;X structure:X:1::60::::: XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX* P1;Y1 structure:Y:1::50::::: YYYYYYYYY-----YYYYYYYYYY-----YYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYY* P1;Y2 structure:Y:1::50::::: YYYYYYYYY-----YYYYYYYYYY-----YYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYY* P1;Y3 structure:Y:1::50::::: YYYYYYYYY-----YYYYYYYYYY-----YYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYYY* P1;target sequence:target:::::::: TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT*

In this case Y would have three times the weight of X in the non-loop regions.

I hope this helps.

Best Wishes,

Roberto

-- Roberto Sanchez | phone : (212) 327 7206 The Rockefeller University | fax : (212) 327 7540 1230 York Avenue, Box 38 | e-mail: sancher@rockvax.rockefeller.edu New York, NY 10021-6399 | http://salilab.org

Graham tyrrell wrote: > > Dear Modellers, > > I am attempting to use Modeller to model a number of loops into a very > large protein system, and am having a few problems. (I am relatively new > > to Modeller so please excuse any dumb questions) > > I have 4 suitable structures which I wish to use as templates for the > missing loop regions in my main structure. The problem I have is that I > want to constrain the coordinates of my model to a greater extent > towards > that of the template which has the loops missing, I then want to use the > > remaining templates to build in the loops. > > This seems a similar problem to one described in the FAQ: > ('5. I don't want to use one region of a template for construction of my > model') > however, due to the large number of loops missing, > and the length of my sequence (~1000 residues) this would be extremely > laborious, with plenty of room for error. > > I was wondering if anyone had any similar experience, and could advise > me > as to an appropriate strategy. > > Regards, > > Graham Tyrrell > > -- > ---------------------------------------------------------------------- > Graham Tyrrell Email (Work) : tyrrell@yorvic.york.ac.uk > (Personal) : gpt103@york.ac.uk > > Telephone : (01904) 432550 > -----------------------------------------------------------------------