A mixture between mathematical significance and biological significance
as a part of the reply:
you should also take into account the thermal vibrations of the atoms
present in that domain, i.e. the "thermal ellipsoids" when you have one
of the representations of anisotropic temperature factors (when these
can be obtained, high enough resolution), together with the associated
density smearing. Especially if you observe correlated thermal
ellipsoids. If you have a small "motion" but that this motion can be (at
least in good part) "explained" by the inherent thermal "flexibility" of
all atoms in that domain then perhaps you can question the significance
of this domain motion (at least in the publication).
Fred.
Filip Van Petegem wrote:
> Dear crystallographers,
>
> I have a general question concerning the comparison of different
> structures. Suppose you have a crystal structure containing a few
> domains. You also have another structure of the same, but in a
> different condition (with a bound ligand, a mutation, or simply a
> different crystallization condition,...). After careful
> superpositions, you notice that one of the domains has shifted over a
> particular distance compared to the other domains, say 1-1.5
> Angstrom. This is a shift of the entire domain. Now how can you
> know that this is a 'significant' change? Say the overall resolution
> of the structures is lower than the observed distance (2.5A for example).
>
> Now saying that a 1.5 Angstrom movement of an entire domain is not
> relevant at this resolution would seem wrong: we're not talking about
> some electron density protruding a bit more in one structure versus
> another, but all of the density has moved in a concerted fashion. So
> this would seem 'real', and not due to noise. I'm not talking about
> the fact that this movement was artificially caused by crystal packing
> or something similar. Just for whatever the reason (whether packing,
> pH, ligand binding, ...), you simply observe the movement.
>
> So the question is: how you can state that a particular movement was
> 'significantly large' compared to the resolution limit? In
> particular, what is the theoretical framework that allows you to state
> that some movement is signifcant? This type of question of course also
> applies to other methods such as cryo-EM. Is a 7A movement of an
> entire domain 'significant' in a 10A map? If it is, how do we quantify
> the significance?
>
> If anybody has a great reference or just an individual opinion, I'd
> like to hear about it.
>
> Regards,
>
> Filip Van Petegem
>
> --
> Filip Van Petegem, PhD
> Assistant Professor
> The University of British Columbia
> Dept. of Biochemistry and Molecular Biology
> 2350 Health Sciences Mall - Rm 2.356
> Vancouver, V6T 1Z3
>
> phone: +1 604 827 4267
> email: [log in to unmask] <mailto:[log in to unmask]>
> http://crg.ubc.ca/VanPetegem/
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