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: [email protected] <mailto:[email protected]>
http://crg.ubc.ca/VanPetegem/
