Protein folding problem solved?

S.A.T. Haldane sah at .dl.ac.uk
Sun Jun 11 08:03:57 EST 1995


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

>> Given that the crystal is a somewhat artificial environment,
>
>  Sorry, can't let you get away with saying that - too many people 
>will believe what you're saying.  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? The crystal structure may represent one possible solution
conformation, or it may represent an artifact of crystallisation which is
significantly different from any normal solution structure. In any case, the
structure in solution is highly flexible in most proteins. Reliance on crystal
structures as a source of solution structures leads to the false idea that 
proteins have only rigid structure in solution. It seems far more internally
likely that proteins are undergoing constant comformational change. In 
particular, crystallisation pins down any flexible regions of protein such
as loops or hinges. 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.

Samuel Haldane










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