1/ Theoretically, yes it seems valid but you will be confronted to
several issues. 2 main ones could be:
a/ You have to see if the active site is more conserved that the
overall protein, don't expect to bind correctly a ligand in a pocket
that share a low identity with your template (it also depends on your
definition of low identity!).
For example, in a case of Kinase, it is common to have low identity
between the kinase (overall of 30-40%) but the ATP binding site, which
is very often targeted in drug design, share a much higher identity (70
b/ If your active site identity is not that an issue, you may need
rearrangement of the side chain in order to bind correctly the ligand.
But Modeller derived homology restraint from the template which doesn't
have the ligand (I presume), therefore these restraints may become a
problem for your optimization, especially side chain - side chain
In that case I will suggest you 2 approaches:
- you can delete the side chain - side
chain restraints for the active site.
- Build you model without the ligand and
dock it after using a docking software.
Now if you template as the same ligand bound into it and you have just
some mutation in your active site therefor: Yes you can use your idea.
And to add a small ligand check the FAQs on the manual, you will find
Eric Feyfant, Ph.D.
Senior research Scientist
200 Cambridge Park Drive
Cambridge, MA 02140
tel: +1 617 665 5656
fax: +1 617 665 5682
>>> Nataraj Balkrishnan <natarajmtech(a)yahoo.co.uk> 3/29/2004 1:11:10 PM
I modelled a protein from low identies template,and more I am having
the idea of location of active site for my modelled protien for
particular ligands. Since I know the active site of the model, I want to
construct the sidechain of aminoacids involved in that active site,by
adding ligand in that particular location.(Since I belive that the
configuration of sidechain in the state of interaction with ligand would
be the actual conformation of the sidechains of active site).
Now my questions are
1)Wheather my this idea is theoreticaly correct ?
2)if the answer for my question 1 is correct, what is the way or
routine which I can use it for adding my ligand(small molecule,eg.,DDT)
to my model?
Kindly help me...
Thank you in advance.
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