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
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