Question:
While it is perhaps understandable that reviewers may not always have
sufficient information to evaluate the quality of the interpreted model
(and must trust that authors have acted in good faith in representing
omit maps, etc.), is it not reasonable to expect reviewers to comment on
the reasonableness of the molecular interactions between posited ligands
and the protein? Crystallography methodology aside, a common thread in
many of these structures, including the 6MOx series, is a paucity of
sensible intermolecular interactions between ligands and protein.
Wouldn't most reviewers comment on these unusual or missing
intermolecular interactions, or note the lack of discussion about the
nature of the ligand-protein interactions? The PIs and relevant
co-authors should have been cognizant of this aspect of the structures
as well, prior to submission for publication. LIgands don't bind to
proteins by magic. There has to be some chemistry there.
In these cases, it looks like there may have been a failure in oversight
on at least two levels.
_____________________________________
Roger S. Rowlett
Gordon & Dorothy Kline Professor, Emeritus
Department of Chemistry
Colgate University
email: rrowl...@colgate.edu
On 7/24/2019 7:36 AM, Rhys Grinter wrote:
Hi All,
Thanks for all the helpful comments and discussion surrounding my last
post. I've been doing a little more investigation into this issue and
wanted to see if people were able to provide me with some additional
opinions/insights.
I investigated the PDB entries for the lead deposition author of the
6MO0-1-2 series: Lin, Y.-L.
(http://www.rcsb.org/pdb/results/results.do?tabtoshow=Current&qrid=50E454B).
With some slightly alarming results.
A number of additional entries appear to have ligands associated with
questionable density.:
6VB0,1,2,3,4 and 6BUY – Density does not support amino acids modelled
and there are questionable interactions with protein and solvent
(Published Scientific Reports 2017)
4NZ8, 4NAQ – Questionable density for peptide modelled,
bad/unrealistic interactions with protein (Published PNAS 2012)
4HOM – Questionable density for peptide modelled. Fo-Fc map density on
refinement seems more interconnected than would be indicated by water,
however density does not fit peptide modelled. Bad/unrealistic
interactions with protein observed, specifically Phe7 of peptide
(chain B) (Published PNAS 2012, same paper as 5NZ8 and 4NAQ)
4KXD et. al. – Questionable density for amino acids in both EDS maps
and re-refined with SF and model minus ligand. Poor R-factors obtained
for 4KXD on refinement (W 0.27,F 0.33) (Published JBC 2013)
These constitute many of entries associated with this author (some
other not mentioned appear are okay) and it makes it seem much less
likely to me that modelling of the structures from my previous post
are a result of lack of experience or poor supervision.
It is in my opinion a huge problem for the field and science in
general, if structures like this are making it into publications in
well respected journals.
Best Wishes,
Rhys
--
Dr Rhys Grinter
NHMRC Postdoctoral Researcher
Monash University
+61 (0)3 9902 9213
+61 (0)403 896 767
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