Dear Enrico, Frank and colleagues,
I am glad to have suggested that everyone's views on this issue should
be aired out on this BB rather than sent off-list to an IUCr committee
member: this is much more interactive and thought-provoking.
There would seem to be clear biases in some of the positions - for
instance, the statement that we overvalue individual structures and that
there is value only in their ensemble has to be seen to be coming from
someone in a structural genomics centre ;-) . However, as Wladek pointed
out, when an investigator's project is crucially dependent on a result
embodied in a deposited structure, it would be of the greatest value to that
investigator to be able to double-check how reliable some features of that
structure (especially its ligands) actually are.
On the other hand Enrico, as a specialist of crystallisation and
modelling, sees value only in improving those contributors to the task of
structure determination. This is forgetting (1) an essential capability of
crystallography: that, through experimental phasing, it can show you what a
protein looks like even if you have never seen nor modelled one before,
through the wondrous process of producing model-free electron-density maps;
and (2) an essential aspect of the task of structure determination: that it
doesn't aim at producing a model with perfect geometry, but one that best
explains the measured data and neither under- nor over-interprets them (I
realise, though, that Enrico's statement "Data just introduces experimental
errors into what would otherwise be a perfect structure" is likely to be
tongue-in-cheek ...).
When it comes to making explicit the advantages of archiving at least
the raw images that yielded the data against which a deposited PDB entry was
refined, many good reasons have been given, but I feel that
(1) there is an over-emphasis on the preservation of diffuse scattering
that has a tendency to give this archiving a nuance of "blue-skies" research
and thus to detract from its practical urgency; time will come for diffuse
scattering to be fully appreciated, but at the moment its mention acts as a
bit of a distraction, if not a turn-off in this context for people who not
not love it already;
(2) as far as I see it, the highest future benefit of having archived
raw images will result from being able to reprocess datasets from samples
containing multiple lattices ("non-merohedral twinning"). Numerous
structures are determined and refined against data obtained by integrating
only the spots from the major lattice, without rejecting those that are
corrupted by overlap by a spot from a minor lattice. This leads to
systematic errors in these data that may only be incompletely taken out by
outlier rejection at the merging stage, and will create noise or confusing
residual features in difference maps, if not false features in the main map
and therefore its interpretation by the model. In my opinion it will be the
development of methods for dealing with overlapped lattices and for the
proper treatment of such data in scaling and refinement (as is already
possible with small molecules) that will bring about the major possibility
of substantially improving deposited results by reprocessing the raw images
co-deposited with them;
(3) there is also the more immediate possibility of better removing ice
rings, or ligand powder rings, from images, than by having to throw away
certain thin shells of merged data in the structure factor file.
I see the case for raw image deposition as absolutely compelling,
especially in view of the auto-catalytic process through which their
availability will speed up the development of precisely the new methods and
software to extract better data from them and better refine models against
them. The impact of structure factor deposition on the development of better
refinement programs is there to prove that this paradigm of a chain reaction
makes total sense.
Various arguments tend to be fired off as decoys - "get better
crystals", why not "get a better post-doc"? - but they are unhelpful in the
way they prolong procrastination when what we need is to bite the bullet.
The IUCr Forum that John Helliwell pointed at already contains draft plans
for a pilot run of a reasonable scheme.
With best wishes,
Gerard.
--
On Tue, Oct 18, 2011 at 06:19:27PM +0200, Enrico Stura wrote:
> Dear Peter,
>
> How many crystallographers does it take to transform bad data into good
> data?
> None, you need a modeller. Only a modeller can give you a structure with
> perfect
> geometry. Data just introduces experimental errors into what would
> otherwise be a perfect
> structure.
>
> If you have good data do you need crystallographers?
> ...
>
> Of course there all the cases in between. That ... you are right, is the
> other half of the story.
>
> From a biological point of view, only borderline cases make "cents" ($+€)
> to store.
> The experimenter in consultation with a beamline scientist at an SR
> facility is the best
> small commitee suitable to evaluate what is worth keeping. I am sure that
> the images
> that are worth storing for a long long time would fit on a few Tb at a
> reasonable cost.
> Storing everything would make it harder to find something worth improving
> in the future.
>
> Enrico.
>
>
> On Tue, 18 Oct 2011 17:12:42 +0200, Peter Keller
> <pkel...@globalphasing.com> wrote:
>
>> Dear Enrico,
>>
>> Please don't get me wrong: what you are saying is not incorrect, but it
>> is only half the story.
>>
>> On Tue, 2011-10-18 at 15:13 +0200, Enrico Stura wrote:
>>> With improving techniques, we should always be making progress!
>>
>> Yes, of course!
>>
>>> If we are trying to answer a biological question that is really
>>> important,
>>> we would be better off
>>> improving the purification, the crystallization, the cryo-conditions
>>
>> You have left X-ray crystallography out of this list. It is a technique
>> like the others, and can also be improved :-)
>>
>> It may be true that the number of crystallographers that are working on
>> improving instrumental methodology and software is small compared to the
>> number working on improving wet-lab techniques, but that number is not
>> zero, and the contribution is significant. The rest of you benefit from
>> that work!
>>
>>> instead of having to rely on
>>> processing old images with new software.
>>>
>>> I have 10 years worth of images. I have reprocessed very few of them and
>>> never made any
>>> sensational progress using the new software. Poor diffraction is poor
>>> diffraction.
>>
>> Maybe so, but certain types of datasets are useful for methods and
>> software development, even if no new biological insights could be gained
>> by reprocessing them. These datasets are often hard to get hold of in
>> practice, especially when they are in someone's lab on a tape that
>> no-one has a reader for any more.
>>
>> Obtaining protein, growing crystals and collecting new data in such a
>> way that the interesting features of those datasets are reproduced can
>> be much much harder than curating the images would be. This is
>> especially true for software-oriented people like us who don't have
>> regular access to wet-lab facilities.
>>
>>> Money can be better spent buying a wine cellar, storage works for wine.
>>
>> Images have already been lost that ought to have been kept. The
>> questions are: how to select the datasets that are potentially of value,
>> and how to make sure that they don't disappear.
>>
>> Regards,
>> Peter.
>>
>
>
> --
> Enrico A. Stura D.Phil. (Oxon) , Tel: 33 (0)1 69 08 4302 Office
> Room 19, Bat.152, Tel: 33 (0)1 69 08 9449 Lab
> LTMB, SIMOPRO, IBiTec-S, CE Saclay, 91191 Gif-sur-Yvette, FRANCE
> http://www-dsv.cea.fr/en/institutes/institute-of-biology-and-technology-saclay-ibitec-s/unites-de-recherche/department-of-molecular-engineering-of-proteins-simopro/molecular-toxinology-and-biotechnology-laboratory-ltmb/crystallogenesis-e.-stura
> http://www.chem.gla.ac.uk/protein/mirror/stura/index2.html
> e-mail: est...@cea.fr Fax: 33 (0)1 69 08 90 71
--
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