Dear Randy
These are very valid points, and I'm so glad you've taken the
important step of initiating this. For now I'd like to respond to one
of them, as it concerns something I and colleagues in Australia are
doing:
The more information that is available, the easier it will be to
detect fabrication (because it is harder to make up more
information convincingly). For instance, if the diffraction data
are deposited, we can check for consistency with the known
properties of real macromolecular crystals, e.g. that they contain
disordered solvent and not vacuum. As Tassos Perrakis has
discovered, there are characteristic ways in which the standard
deviations depend on the intensities and the resolution. If
unmerged data are deposited, there will probably be evidence of
radiation damage, weak effects from intrinsic anomalous scatterers,
etc. Raw images are probably even harder to simulate convincingly.
After the recent Science retractions we realised that its about time
raw data was made available. So, we have set about creating the
necessary IT and software to do this for our diffraction data, and
are encouraging Australian colleagues to do the same. We are about a
week away from launching a web-accessible repository for our recently
published (eg deposited in PDB) data, and this should coincide with
an upcoming publication describing a new structure from our labs. The
aim is that publication occurs simultaneously with release in PDB as
well as raw diffraction data on our website. We hope to house as much
of our data as possible, as well as data from other Australian labs,
but obviously the potential dataset will be huge, so we are trying to
develop, and make available freely to the community, software tools
that allow others to easily setup their own repositories. After
brief discussion with PDB the plan is that PDB include links from
coordinates/SF's to the raw data using a simple handle that can be
incorporated into a URL. We would hope that we can convince the
journals that raw data must be made available at the time of
publication, in the same way as coordinates and structure factors.
Of course, we realise that there will be many hurdles along the way
but we are convinced that simply making the raw data available ASAP
is a 'good thing'.
We are happy to share more details of our IT plans with the CCP4BB,
such that they can be improved, and look forward to hearing feedback
cheers
Ashley Buckle and James Whisstock
If a structure is fabricated by making up a new crystal form,
perhaps a complex of previously-known components, then the crystal
packing interactions should look like the interactions seen in real
crystals. If it's fabricated by homology modelling, then the
internal packing is likely to be suboptimal. I'm told by David
Baker (who knows a thing or two about this) that it is extremely
difficult to make a homology model that both obeys what we know
about torsion angle preferences and is packed as well as a real
protein structure.
I'm very interested in hearing about new ideas along these lines.
The wwPDB has agreed to sponsor a workshop next year where we will
propose and test new validation criteria.
4. If new validation criteria are applied at the PDB, won't someone
who wants to fabricate a structure just keep improving their
fabricated model until it passes all the tests?
That's a possibility, but I think the deterrence effect of knowing
that there are measures to detect fabrication will outweigh this.
And it isn't enough for a fabricated structure to pass today's
tests; it has to pass all the new tests devised for the rest of the
person's life, or at least their career.
5. What should we do if tests suggest that a structure may be
fabricated?
I think we need to be extremely careful. Conclusions should not be
drawn on the basis of a few numbers. The tests can just point up
which structures should be examined closely. Close examination
would then involve less automated criteria, such as whether the
structure agrees with all the biochemical data about the system. As
in the process followed by Nature, you also have to start by giving
the people who deposited the structure an opportunity to explain
the anomalies.
Randy Read
*NOTE* My new tel. no: (03) 9902 0269
Ashley Buckle Ph.D
NHMRC Senior Research Fellow
The Department of Biochemistry and Molecular Biology
School of Biomedical Sciences, Faculty of Medicine &
Victorian Bioinformatics Consortium (VBC)
Monash University, Clayton, Vic 3800
Australia
http://www.med.monash.edu.au/biochem/staff/abuckle.html
iChat/AIM: blindcaptaincat
skype: ashley.buckle
Tel: (613) 9902 0269 (office)
Tel: (613) 9905 1653 (lab)
Fax : (613) 9905 4699
