Ivan Anishchenko wrote: > I'm a student and not yet rather familiar with Modeller. I've faced > some difficulties when modeling long loops. My target sequences are 35 > residues long and have just slight differences (approximately five > residues) from the template. The only restraint to the models is a > disulfide bond connecting the first and the last residues. Several > known structures (completely different) are used as templates; the > result of the modeling each time are structures similar to the one > used as template. The structures are supposed to be variable: nothing > is known about their preferable conformation. Also there is no > suggestion of elements with definite secondary structure. > > 1) whether it is possible somehow to obtain a set of possible > conformations (not only those similar to the initial ones) by making > changes in initial conditions or with the help of any other means?

Modeller builds models that look like the template by construction, so the only way to get models that don't look like the template is to misalign things. For example, if you have two domains with a 'hinge' between them, you could align your sequence to each domain separately (using two copies of the template) and align the hinge region to gaps in the templates. Then, since you have no inter-residue distances in your model, the two templates will hinge freely. Whether this is applicable to your problem depends on the structures, of course.

> 2) can the tools for loop modeling be applied here, because the length > of the loop seems to be excessive. Taking into account the low > accuracy of the models obtained is it then possible using some > assessment method (DOPE for example) to pick out more reliable models?

Loop modeling is not reliable for loops longer than about 12 residues. Beyond that, you have essentially the same problems as the protein folding guys.

> 3) does the DOPE assessment method have any limitations on the minimal > length of the structure and how does its accuracy change with length > if it does?

It's just an atomistic pair potential, so there's no upper or lower limit on system size. But I can't tell you whether it gives accurate scores for very small structures, because the only way to test that is to look at the performance compared to decoys and native structures, and I doubt we had any very small structures in our benchmark sets (you'd have to check the publications to be sure).

Ben Webb, Modeller Caretaker