Dominika is entirely correct, the F and (especially) sigma(F) values 
are clearly inconsistent with my naive suggestion that columns could 
have been swapped accidentally in an mtz file. 

George

Prof. George M. Sheldrick FRS
Dept. Structural Chemistry, 
University of Goettingen,
Tammannstr. 4,
D37077 Goettingen, Germany
Tel. +49-551-39-3021 or -3068
Fax. +49-551-39-2582


On Thu, 16 Aug 2007, Dominika Borek wrote:

> There are several issues under current discussion. We outline a few of
> these below, in order of importance.
> 
> The structure 2hr0 is unambiguously fake. Valid arguments have already been
> published in a Brief Communication by Janssen et. al (Nature, 448:E1-E2, 9
> August 2007). However, the published response from the authors of the
> questioned deposit may sound to unfamiliar person as an issue of a
> scientific controversy. There are many additional independent signs of
> intentional data fabrication in this case, above and beyond those already
> mentioned.
> 
> One diagnostic is related to the fact that fabricating data will not show
> proper features of proteins with respect to disorder. The reported case has
> a very high ratio of “Fobs”/atom parameters, thus the phase uncertainty is
> small. In real structures fully solvent exposed chains without stabilizing
> interactions display intrinsically high disorder, yet in this structure
> these residues (e.g., Arg932B, Met1325B, Glu1138B, Arg459A, etc.) are
> impossibly well ordered.
> 
> The second set of diagnostics is the observation of perfect electron
> density around impossible geometries. For example, the electron density is
> perfect (visible even at the 4 sigma level in a 2Fo-Fc map) with no
> significant negative peaks in an Fo-Fc map around the guanidinium group of
> Arg1112B, which is in an outrageously close contact to carbon atoms of
> Lys1117B. This observation appears in many other places in the map as well.
> The issue is not the presence of bad contacts, but the lack of disorder
> (high B-factors) or negative peaks in an Fo-Fc map in this region that
> could explain why the bad contacts remain in the model.
> 
> The third set of diagnostics are statistics that do not occur in real
> structures. The ones mentioned previously are already very convincing
> (moments, B-factor plots, bulk solvent issues, etc.). We can add more
> evidence from a round of Refmac refinement of the deposited model versus
> the deposited structure factors. The anisotropic scaling factor obtained,
> which for a structure in a low symmetry space group such as C2 that has an
> inherent lack of constraint in packing symmetry, is unreasonable
> (particularly in view of the problems with lattice contacts already
> mentioned). The values from a Refmac refinement for a typical structure in
> space group C2 are: B11 =  0.72 B22 =  1.15 B33 = -2.12 B12 =  0.00 B13 =
> -1.40 B23 =  0.00 (B12 and B23 are zero due to C2 space group symmetry).
> For structure 2hr0:  B11 = -0.02 B22 =  0.00 B33 =  0.02 B12 =  0.00 B13 =
> 0.01 B23 =  0.00. Statistical reasoning can lead to P-values in the range
> of 10exp(-6) for such values to be produced by chance in a real structure,
> but they are highly likely in a fabricated case.
> 
> The fourth set of diagnostics are significant inconsistencies in published
> methods, e.g. the authors claim that they collected data from four
> crystals, yet their data merging statistics show an R-merge = 0.11 in the
> last resolution shell. It is simply impossible to get such values
> particularly when I/sigma(I) for the last resolution shell was stated as
> 1.32. Moreover, the overall I/sigma(I) for all data is 5.36 and the overall
> R-merge is 0.07 – values highly inconsistent with the reported data
> resolution, quality of map and high data completeness (97.3%).
> 
> Overall this is just a short list of problems, the indicators of data
> fabrication/falsification are plentiful and if needed can be easily
> provided to interested parties.
> 
> We fully support Randy Read's excellent comments with our view of
> retraction and public discussion of this problem:
> 
> “Originally I expected that the publication of our Brief Communication in
> Nature would stimulate a lot of discussion on the bulletin board, but
> clearly it hasn't. One reason is probably that we couldn't be as forthright
> as we wished to be. For its own good reasons, Nature did not allow us to
> use the word "fabricated". Nor were we allowed to discuss other structures
> from the same group, if they weren't published in Nature.”
> 
> One needs to address this policy with publishers in cases of intentional
> fraud that can be proven simply by an analysis of the published results. At
> this point the article needs to be retracted by Nature after Nature's
> internal investigation with input from crystallographic community rather
> then after obtaining results of any potential administrative investigation
> of fraud.
> 
> “Another reason is an understandable reluctance to make allegations in
> public, and the CCP4 bulletin board probably isn't the best place to do
> that.”
> 
> The discussion of fraud allegation was initiated by public reply to a
> question addressed to a single person, so it happened by chance rather than
> by intention, but with no complaint from our side.
> 
> On a different aspect of the discussion – namely, data
> preservation—currently, funding agencies as well as scientific
> responsibility requires authors of any publication to preserve and keep for
> a reasonable amount of time all the primary data for experiments. In the
> case of crystallography, this would reasonably be interpreted to mean
> preservation of X-ray diffraction images. It should be required that
> authors retrieve and provide these data in case of controversy. In any
> case, the key results are deposited in the PDB. As long as structure
> factors are deposited it is effectively impossible to do a credible job of
> fabricating data, as has been discussed.
> 
> G. Sheldrick:” The deposited structure 2HR0 shows all the signs of having
> been refined, deliberately or accidentally, against 'calculated' data. The
> model used to 'calculate' the data had (almost) constant B values in a
> rather empty
> cell containing no solvent. For example, it could have been a (partial?)
> molecular replacement solution obtained using real data. It seems to me
> that it is perfectly possible that two reflection files (or two columns in
> an mtz file) were carelessly exchanged by a crystallographically
> inexperienced researcher.”
> 
> This scenario is impossible. If this had happened, then subsequent
> refinement (which we did) of the structure would produce impossibly low
> R-factors. The calculated structure factors were randomized to prevent this
> occurrence, indicating strongly that it was done intentionally. There are
> more indicators of intentional fabrication/falsification of data. The
> structure factors used in refinement are clearly derived from a model of
> low quality, which suggest a model derived from a low resolution dataset.
> But the most convincing indicator is the form of the response to the Brief
> Communication by Janssen et.al. If it would be any kind of mistake it would
> have to be of a very obvious nature, and the authors would recognize it and
> state it in a public response. Their defense does not make any sense in
> terms of crystallography when combined with inspection of the deposited
> data.
> 
> 
> 
> Dominika Borek
> UT Southwestern Medical Center
> 5323 Harry Hines Boulevard
> Dallas, Texas 75390-8816
> phone: +1 214-645-6378
> fax: +1 214-645-6353
> [log in to unmask]
>