Hi all,
I was asked to assisst in a protein crystallography problem. Apparently
a protein would crystallise with his binding partner but not without. So
I was asked wether I could design a few peptides that help stabilisz the
Protein and could be used for co-crystallisation.
We figured that the loss of the partner could lead to an increse in
flexibility in the binding area, which then prevents crystal formation.
The first logical step was then to start with fragments of 10 residues
of the partner that were in vdw range of the protein and evaluate their
binding energy. Pretty fast I identified a number of peptides that bound
tight to the protein. Not a surprise really, as I just cut them out of a
pdb file and the peptides where already in binding conformation.
Two questions arise however:
A) Is this the only place the peptide would bind? Can alternative sites
be found?
B) Will the peptide really lead to a decrease in flexibility?
Question B can be answered quickly. Just have a long run, to allow for
loop movement, with the protein alone and in complex and have ptraj
calculate flucuations. If a significant decrease can be observed in the
binding area: success.
For A it is different. I could place many peptides in close proximity to
the protein's surface (not just the binding site) and see what happends
during MD. The use of a docking program was also suggested. Are there
programs capable of flexible docking peptides to whole protein?
I really appreciate any thought, idea, suggestion, link or paper you got!
regards
Simon
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Received on Wed Feb 24 2010 - 07:00:03 PST
