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
ii) X-ray structures indicate that all loops have well-defined
conformations, and that the conformations of the loops are
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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