On Wednesday 27 January 2010, John Badger wrote:
> Colin,
>
> Your point:
> "I think the point here (probably the one you are making) is that if
> crystallographers produce a pseudo rigid body motion (or static
> disorder) model described by TLS parameters then it would make specific
> predictions of diffuse scatter. These predictions could be used to test
> the model. In other words data is already there to validate the TLS
> model and this data is being ignored."
> is well taken.
This is also the point made by Peter Moore recently:
On the relationship between diffraction patterns and motions in
macromolecular crystals. Structure (2009) 17:1307
> This is essentially what was done by Caspar, Clarage et al in their work on
> insulin and lysozyme crystals, published in Nature and Proteins.
> Nature 332 659-662 1988
> Proteins 12 145-157 1992
>
> Diffuse scatter patterns were compared to simulations of correlated motions
> that were long-range (say, the size of the whole molecule) and short range
> (say, the size of an amino acid). The TDS data were best fit when the
> majority of the motion was put in the short-coupled range component with a
> much more minor component in the whole-molecule component. i.e. it does
> not seem that TLS models as used to represent most of the B-factor by rigid
> protein motions are consistent with this TDS data.
>
> For that matter, pretty much every type of experimental measurement I know
> of protein dynamics, including those which probe the normal mode spectrum
> directly (inelastic neutron scattering work by Cusack) also put most of the
> motion into high frequency components and deemphasize the low order modes
> (the TLS components). A review of all this is
> Prog.Biophys.Molec.Biol. 63 251-276, 1995.
>
> From this perspective it is quite surprising that crystallographers are so
> keen
> on using TLS models for fitting displacement amplitudes.
I'll play devil's advocate and put forth the contrarian view.
It is not surprising at all that crystallographers are keen on TLS
models. TLS models do an amazingly good job of explaining the results of
an experiment we understand very well - measuring Bragg
diffraction intensities.
The burden of proof may lie on the other side.
If TDS simulations fail to reproduce the scatter measured from
crystals where we already have an excellent physical model for the
contents, perhaps it is because we do not understand, and hence
cannot model, the TDS experiment as well as we understand and model
Bragg diffraction.
I admit to deep ignorance of the underlying physics of TDS.
To remedy this, I am accumulating quite a stack of reading material
that should keep me busy next quarter. When I emerge from the experience,
perhaps I will be able to offer a more insightful perspective.
One point I have noticed previously, however, is that the TLS models
used in some earlier comparative work were incomplete
(used fewer parameters) compared to the ones we use now.
