[modeller_usage] some food for thought...

["Himanshu Grover" <>]

Hullo,
    am a novice user of modeller... need some help for a problem described
below...

my target protein contains 2 chains which need to be modelled. I am
currently modelling them independently and then concatenating their pdbs
to get the complete protein.

Firstly, is is possible to model the 2 chains together, rather than
independently, since that would mean taking one chain into context while
modelling the other...

Secondly, after generating the protein, i need to check its binding to
another protein, with which it is always found complexed. For instance, in
case of immunoglobulins, we have 2 chains to be modelled, and then these
chains are always found complexed with a peptide-MHC... So I need that the
optimization of the chains and loop refinement of the heavy and the light
chains should take place taking into consideration the peptide-MHC as
well.

The reason i want to do this is that I tried to generate the structure of
some xyz protein through modeller, whose crystallographic structure is
also available. so i took xyz(crystallographic) as the template and tried
to generate the same structure with modeller. the new struc. has an rmsd
value of 0.19 as compared to the actual structure, which is quite good.
however, at the binding site, there are some side chains that are not
nicely fitting on top of the actual structure. and some interactions have
gone down, resulting in poor binding. is there a way to rectify this
problem?? i was thinking of doing the simulated annealing part taking into
context the entire complex... that is, say, after we
concatenate the light and heavy chain of immunoglobulin with p-MHC, and
then applying molecular dynamics taking into consideration p-MHC
also...but am not sure whether that is possible or not... any say??

sincerely,
himan...