Sequence/Structure Comparisons

[Simon Brocklehurst]

In article <1993Sep8.161211.6420 at infodev.cam.ac.uk>, smb18 at mbfs.bio.cam.ac.uk (Simon Brocklehurst) writes:
|> Hi,
|>    I thought I might try to initiate a discussion on the net on the
|> topic of Sequence/Structure Comparisons that have been flooding the
|> literature over recent months and years.  The question that I would 
|> like to ask is,
|> 
|>            "How much better is a Sequence/Structure Comparison
|>             than looking at multiple sequence alignments for
|>             prediction of protein structure?"
|> 
|> 

Barbara Moore writes:
>"(1) How much better is a sequence/structure comparison than aligning
>(possibly multiple) sequences to a known-structure sequence?
>
>The claim of the sequence/structure matchers is that they can catch
>structural similarities between proteins whose sequences are very
>different, and therefore a sequence alignment approach wouldn't work.
>Most groups tend to give as examples one or a few such matches.
>Examples: Bowie/Luthy/Eisenberg find such matches between CRP
>and the cAMP-dependent protein kinase family, and between actin and
>HSC70.  Jones/Taylor/Thornton find C-phycocyanin like globins.
>

  OK, can I clarify my question. How much better is a sequence/structure
  comparison than doing the following:

          1)    Take the sequence of the unknown
          2)    Align all other sequences that can be detected
                as being homologous
          3)    Do a "state-of-the-art" secondary structure prediction
                e.g. the Sander "PHD" approach
          4)    See what folds are known that could fit the predicted
                secondary structure


  A simple (but not very good!) example should illustrate this:

           Say we do a 2ndry structure prediction that gives
           four helices.  If we look look all known structures
           and find that the only time four helices occur is
           in a 4-helix bundle then we can guess at the fold.


>Also the sequence/structure matching approach has the potential of
>matching a sequence to an as-yet-unseen structure which has been
>postulated, perhaps by combining pieces of super-secondary structure.
>(Temple Smith's group, for example, discussed this possibility in a
>poster at Waterville Valley.)  This is relevant because there are
>estimates that we've seen a sizable chunk but not all of the possible
>structures.  "

   This could also be done with the multiple alignment/2ndry structure
   prediction approach


   Any comments?  
      
_______________________________________________________________________
Simon M. Brocklehurst
Cambridge Centre for Molecular Recognition
Department of Biochemistry
University of Cambridge
Tennis Court Road
Cambridge
UK

E-mail : smb18 at mbfs.bio.cam.ac.uk