In article <D31CzC.DEL at rockyd.rockefeller.edu> sali at tamika.rockefeller.edu (Andrej Sali) writes:
> In article <1995Jan26.200503.27941 at alw.nih.gov> johnk at spasm.niddk.nih.gov> (John Kuszewski) writes:
> >
> > Once and for all:
> >
> > The folding problem isn't solved!
> >
> > Modelling based on (very) related sequences with known structures is
> > still very difficult and hardly a well-developed technique!
> >
> > Talk to your local crystallographer or NMR spectroscopist
> > if you want coordinates that didn't just come from your
> > imagination.
> > --
> (*** preceding parts of article deleted ***)
> ... When sequence identity is about 40% or more, you can get a model by
> comparative modeling that is essentially equivalent to a medium resolution
> X-ray structure (2.5A; R=factor 25%).
> (*** subsequent parts of article deleted ***)
I'm sorry to have to insert my 2 cents here, but this is COMPLETELY incorrect.
Having worked at a variety of resolutions in crystal structures, and done some
homology modeling myself, I have yet to see a model that corresponded to
anything better than a partially-refined 4.5 Angstrom resolution structure
(read this as approx. 3x the error level that Dr. Sali suggests).
I think that the term "essentially equivalent" is being stretched way too far
here - the overall fold will be correct, some conserved loops will
perhaps even be correct, but many of the side-chains and a significant portion
of the backbone will exhibit very substantial deviations from their "true"
positions.
If one wants an *accurate* picture of one's molecule one should (to quote
John Kuszewski)
> Talk to your local crystallographer or NMR spectroscopist
> if you want coordinates that didn't just come from your
> imagination.
If one wants a rough idea of what one's structure might be *similar* to,
then one should just find something with known structure that has 40% or
more sequence identity to the target and take a look at it. I'm tempted to
beleive that half the world has homology to immunoglobulins and the rest to
proteases, anyway :) <--- note the smiley...
I've heard claims that modeling could approach the resolution of crystal
structures for many, many years. I have yet to see anyone live up to that
claim.
Just couldn't let this one go by.....
Phil Jeffrey (a protein crystallographer)
--
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| Phil Jeffrey | |
| X-ray/Computer Manager, Crystallography Lab | If you lie to the compiler, |
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|phil at xray2.mskcc.org, p-jeffrey at ski.mskcc.org | - Henry Spencer |
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