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On Thursday 24 August 2006 07:52 am, Mischa Machius wrote:
>
> Now, it is not at all prohibitive to calculate multiple structures,
> even at low resolution. Provided the number of fitted parameters was
> chosen appropriately, we could simply ask, "What are ALL the
> structures that are ideal in terms of geometry and that also best fit
> to the determined atomic positions?" Just like NMR people do it. We
> can simply run many independent refinements using simulated
> annealing, or some other randomizer, and calculate all structures
> that are within kT or some other criterion. We would not violate any
> data/parameter ratio rules, because we are not refining the
> structures simultaneously. Every single structure would still be
> ideal in terms of geometry, and all structures taken together as an
> ensemble would well describe the (averaged) crystal structure. We
> would then use rmsd's to describe deviations between all ideal
> structures that fit the data, just like in NMR, and get rid of the
> confusing rmsd's for bond lengths and angles.
>
> Misconceptions?
I would argue that use of multi-group TLS models accomplishes
the same goal, with a HUGE advantage in the number of parameters
required.
Yes, your crystal samples both static and dynamic disorder,
and the measured diffraction data are due to an average over
the states present in the sample. But to the extent that
the states accessible to the protein are adequately approximated
by an expansion of rigid-body motion about the average structure,
the is exactly the ensemble of states modeled by TLS.
Larger deviations start to violate the rigid-body approximation,
but then again larger deviations are less likely to be tolerated
by the crystal lattice, and hence are not likely to be present
in your crystal.
On top of that, the multi-group TLS model is in and of itself
an informative description of the observed protein flexibility,
whereas a long list of rmsd's for the superposition of
NMR-like ensemble members is at least one step away from obvious
interpretation.
EAM
--
Ethan A Merritt
Biomolecular Structure Center
University of Washington, Seattle WA
