Protein folding problem solved?

Simon Brocklehurst Bioc smb18 at mole.bio.cam.ac.uk
Mon Jun 12 06:53:50 EST 1995


sah at .dl.ac.uk (S.A.T. Haldane) writes:

>smb18 at mole.bio.cam.ac.uk (Simon Brocklehurst (Bioc)) wrote:

>>Crystal structures of proteins are, for the most part, excellent models 
>for the structure in solution.

>I'm sorry, but I find this assertion very hard to believe. Where is the
>evidence for it?
  
Ummm...   there's plenty of proteins for which three-dimensional, time-averaged
models have been obtained by both X-ray crystallography and solution homo and 
heteronuclear magnetic resonance spectroscopy.  Comparisons show that the 
structures obtained from both techniques are basically the same.

> In any case, the structure in solution is highly flexible in most proteins. 

  Some parts of proteins are flexible, some aren't, and time-scales of motions
are variable.  This isn't particularly relevant to the argument though.

> Reliance on crystal structures as a source of solution structures leads to 
> the false idea that proteins have only rigid structure in solution. 

  Not at all.  Why do you think that?

> In particular, crystallisation pins down any flexible regions of protein 
> such as loops or hinges.

  It _can_ do, but this isn't generally true.

> Crystal structures should be used as guides to the solution structure only 
> with a hefty pinch of salt, and preferably where confirmatory evidence is 
> available, such as solution X-ray scattering, NMR, CD, etc.

 This doesn't mean a whole lot.  Anyway, what does solution scattering and 
CD have to do with this?

   If anyone believes that:

               i) all loops in proteins are highly flexible
 and
              ii) X-ray structures indicate that all loops have well-defined 
                  conformations, and that the conformations of the loops are
                  wrong anyway,

then they're a long way off the mark.
_____________________________________________________________________________
|
|  ,_ o     Simon M. Brocklehurst,
| /  //\,   Oxford Centre for Molecular Sciences, Department of Biochemistry,
|   \>> |   University of Oxford, Oxford, UK.
|    \\,    E-mail: smb at bioch.ox.ac.uk | WWW: http://www.ocms.ox.ac.uk/~smb/
|____________________________________________________________________________







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