If it is as it appears, it is disappointing to see this in JACS. I would
expect better. Unfortunately, reviewers don't always get a lot of
information to judge quality of structures (which has been discussed
extensively on prior occasions on this board), so some trust is
involved that what data is presented by the authors is representative. I
see the authors duly presented a 2Fo-Fc map and a Fo-Fc omit map in one
of the figures, but it appears from a personal examination that the
Fo-Fc omit map presented may not resemble what one gets when personally
examining the deposited data, and some protein chain refinement problems
are immediately evident. That is a bit concerning. High-pressure
research, coupled with (perhaps) a lack of understanding, experience,
and supervision is a potentially dangerous ethical stew.
Correcting erroneous published data is challenging. I share the
frustration of others when attempting to challenge scientifically
questionable published results. My trip down the rabbit hole (not
related directly to crystallography) nearly identical to that related
previously here. Spend your own time writing a full paper rebuttal (ugh)
or move on and concentrate resources on your own work.
_____________________________________
Roger S. Rowlett
Gordon & Dorothy Kline Professor, Emeritus
Department of Chemistry
Colgate University
email: rrowl...@colgate.edu
On 7/19/2019 2:24 PM, Robbie Joosten wrote:
Even though PDB-REDO cannot salvage this model without extensive
rebuilding which is what Tristan showed, it is fun to look at the maps
and B-factors near the ligand. The B-factors go way up and the
negative difference density disappears, as does most of the 2mFo-DFc
density. It’s obviously not news to most people on the CCP4BB,
properly refining B-factors is really important!
Cheers,
Robbie
*From:*CCP4 bulletin board [mailto:CCP4BB@JISCMAIL.AC.UK] *On Behalf
Of *Bärbel Blaum
*Sent:* Friday, July 19, 2019 17:24
*To:* CCP4BB@JISCMAIL.AC.UK
*Subject:* Re: [ccp4bb] Questionable Ligand Density: 6MO0, 6MO1, 6MO2
Hi Rhys,
the reported B-factors for the “ligands” are all way below the
reported B-factors for the protein chains, with the worst of the three
complexes reporting unitless numbers 23.2 and 64.8, respectively, just
to highlight *one* striking feature of the data collection and
refinement table. So even with the limited info normally available to
reviewers this table should have raised a red flag. After the
re-refinement suggested by others, i.e. your own proper assessment of
the crystallographic data, if you do not find noteworthy density you
may want to contact the article’s editor with your results. If you
work in this field, i.e. really care about this paper scientifically
and you are not afraid to confront the authors you could suggest
writing a comment/direct response article but in my opinion that would
only make sense if you can be sure beforehand that it will be linked
visibly to the actual paper, else it will be a waste of time. And
don’t forget that just because one or some of the authors did a bad
job at the crystallographic end other findings of the paper might
still be solid – in collaborations often one author is unable to
critically evaluate another author’s contribution and this would not
be the first case were good synthetic or biological work is presented
along with a bad crystal structure.
By the way and a bit ironically this protein may have suffered bad
crystallography/scientific practice before - I think it was one of the
fake Krishna Murthy structures, right? The associated (now retracted)
article I mean is here
https://www.sciencedirect.com/science/article/pii/S002228360093924X?via%3Dihub
Kind regards, Bärbel
---
Bärbel Blaum, PhD
Inthera Bioscience AG
Einsiedlerstrasse 34
CH-8820 Waedenswil
Switzerland
E-Mail: baerbel.bl...@intherabio.com
Phone: +41 43 477 94 72--
*Von: *CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> im Auftrag von
"Manfred S. Weiss" <manfred.we...@helmholtz-berlin.de>
*Antworten an: *"Manfred S. Weiss" <manfred.we...@helmholtz-berlin.de>
*Datum: *Freitag, 19. Juli 2019 um 16:03
*An: *<CCP4BB@JISCMAIL.AC.UK>
*Betreff: *Re: [ccp4bb] Questionable Ligand Density: 6MO0, 6MO1, 6MO2
Hi Rhys,
all three structures are at modest resolution and they don't seem to
be properly refined. At least they are all below average. I wonder
how this paper made it past the referees.
I haven't checked the paper, but there are ways and means how to
deal with weakly bound ligands in the best possible way. One aspect
is to improve the phases as much as possible without having the ligand
present. This was obviously NOT done. Another way is to use the
PANDDA approach, which relies on having many data sets available.
I suppose that this was also not done.
The best way to check is to delete the ligand and so some extensive
refinement in order to remove the phase bias introduced by the
ligand. Only then you can reliably assess whether something is there
or not.
Cheers, Manfred
Am 19.07.2019 um 15:21 schrieb Rhys Grinter:
Hi All,
I was chatting with a colleague during a recent synchrotron visit
and they'd recently come across some ligand/drug bound structures
associated with a paper recently published in a high impact factor
journal.
They had pulled the associated SFs from the PDB and found that the
electron density associated with these ligands didn't match that
reported in the paper and certainly wasn't sufficient to model the
alleged ligand.
I also pulled the structure factors and after refinement in the
presence/absence of the alleged ligand I also feel that the
density present does not warrant modelling of the ligand.
I was hoping that the community might be able to give me an
outside opinion on these datasets (PDB IDs: 6MO0, 6MO1, 6MO2) and
if the problem associated with the data is verified, provide some
advice on how to proceed.
This isn't the first occasion I've seen ligand bound structures
with questionable density deposited in association with papers in
well respected journals. Despite improvements to validation I feel
that this problem is widespread.
Best Regards,
Rhys
--
Dr Rhys Grinter
NHMRC Postdoctoral Researcher
Monash University
+61 (0)3 9902 9213
+61 (0)403 896 767
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--
Dr. Manfred S. Weiss
Macromolecular Crystallography
Helmholtz-Zentrum Berlin
Albert-Einstein-Str. 15
D-12489 Berlin
Germany
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