Help for a rookie? (peptide sequences)

[Wayne R. Baker]

In bionet.molbio.proteins,  Mark Haythorn <MHAYTHOR at ix.netcom.com> wrote
:johnk at spasm.niddk.nih.gov (John Kuszewski) wrote:
:
:>|> I've been given a 5-amino acid sequence and need to make a
:>|> 3-dimensional picture of it.  Suppose I had Phe-Ala-Glu-Val-Tyr; what
:>|> would it look like in 3-D?  What if I added a hydroxly group or a
:>|> Fluorine to one of the amino acids?  What would it do?
:
:>Peptides that short are usually very flexible--very few have any 
:>sort of structure in solution.
:
:>Any 3-d "structure" you get by any method (other than experiment)
:>is likely to be meaningless.
:
:Suppose I came up with a 5-6 or even 8-amino acid peptide and it
:appeared to have the ability to bind to a biological receptor.  Could
:I then 'model' the peptide and get an accurate conformation?  It
:doesn't sound like it...  

  While it is unlikely a small peptide has structure, it's not
impossible. Dyson had a hexapeptide with a define turn structure. 

  If you wanted a quick and dirty answer and had the structure of the
receptor as well as a highly defined ligand site, you could conceivably
model the peptide in. But it would still be a model and not a structure.
Implicit in this method is the assumption that the receptor has the same
structure in both the apo and holo forms, which probably isn't correct. 

:If I synthesized a peptide, I would have to
:be able to prove that what I made is in fact what I think I
:synthesized. It sounds to me like this is NOT an exact science-  for
:reasns you mentioned above (flexibility in solution).

  Depending on your binding kinetics, transfer NOE NMR experiments could
give you the structure of the peptide bound to the receptor. Take a look
in Wuthrich's book and the references cited. If you can use these
methods, you will have the structure of the bound form that is valid
(which is what I take the first sentence in your paragraph above to
mean). 

Wayne Baker (baker at iastate.edu)		Maybe a great magnet pulls
Biochemistry & Biophysics		All souls towards truth
Iowa State University			-- k. d. lang, "Constant Craving"