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Re: new user and domain movements


> Dear Modellers,
>         I am a new user of modeller having just completed my PHD in X-ray crystallography. I have two questions about modeller.
>         1) Do the template positions of domains in space, for multidomain proteins, have to always be pre-arranged/aligned by me to the approximate postions of the putative model before running modeller ?


>         2) In a way this is similar to the first question. How can I model the possible linker flexibility in a diabody ?
> I would need to fix the atom positions in each Fv with respect to each other but not thier actual coordinates, whilst allowing a variety of linker models to be built.

if you use loop modeling it assumes that the stem residues and
environment (i.e. the two domains) are fixed, and only the loop is
optimized. The domains do not  move with respect to each other. Modeller
uses the interdomain nonbonded distance restraints as they are derived
from the input conformation, i.e. the domain orientation does not change
too much  during modeling.

if you are looking for domain movement modeling: Modeller is not a
trivial tool for that, but it is possible. A  quick and dirty solution
is to break up your template into two, non overlapping  parts, at the
linker site, and use them as separate templates. By this way modeller
will not derive interdomain restraints, because there is no overlap.
However the outcome of modeling, especially with longer linker regions,
can be quite  uncertain. This is a kind of 'ab initio' modeling of
domain placement.

Andras Fiser, PhD            # phone: (212) 327 7216
The Rockefeller University   # fax:   (212) 327 7540 
Box 270, 1230 York Avenue    # e-mail:
New York, NY 10021-6399, USA # http://salilab.org/~andras