John, Ethan
Some good points being made regarding the discrepancy between TLS models
and measured diffuse scatter. However, as James has pointed out,
measuring the diffuse scatter is not that easy due to the contribution
of the lattice  This could be why there are some problems as large
motions (dynamic or static) are likely to be correlated across unit
cells.

However, I think one should be able to sort this out for the following
cases

1. Complete correlation within any block/domain, with another structure
in adjacent domains. In these cases, the domains and unit cell
dimesnsions will be different and we can simply pick them up with a high
resolution diffraction instrument (e.g. similar to a topographic or a
coherent diffraction imaging set up)
2. No correlation - unit cells dimensions the same but contents
different (e.g. due to  thermal motion, static disorder) Gives diffuse
scatter well separated from the Bragg peaks. This can be measured.
3. Somewhere between the two. Use combination of above techniques.
 
If there are fringes from the blocks/domains, this is extra information
which can be used.
 
All very trivial (or not).
I know about the Caspar, Clarage et al work but must re read it. Thanks
for the reference to Peter Moores' paper.

Cheers
  Colin
 



> -----Original Message-----
> From: CCP4 bulletin board [mailto:[log in to unmask]] On 
> Behalf Of Ethan Merritt
> Sent: 28 January 2010 07:35
> To: [log in to unmask]
> Subject: Re: [ccp4bb] Refining against images instead of only 
> reflections
> 
> 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.
> 

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