I'm going to dive back in here again to expand this discussion.
Whether this diversion clarifies or obscures issues surrounding the
"crystallographers' dilemma" I'll leave for others to decide.
There is currently considerable discussion, among people who care
about cell phone cameras, over the behavior of the cameras in some
Samsung cell phones when photos are taken that include the Moon.
https://www.reddit.com/r/Android/comments/11nzrb0/samsung_space_zoom_moon_shots_are_fake_and_here/
In this post, evidence is presented that photos taken with one of
these phone cameras, and includes the Earth's largest satellite, the
image shows a properly exposed and detailed image of the orb. This
despite the fact that the test photograph described in the post is of a
tableau containing a deliberately blurred photo of the cratered globe.
The claim is made that the Samsung app is adding information from
sources other than the camera's light sensor and therefore the image is
"fake".
I expect that Samsung would reply that, once the app is confident
that the silver disk in the image is the nighttime traditional symbol of
romance, it is perfectly reasonable to make that, now identified aerial,
phenomenon appear in the image as expected by every sighted human in the
history of our species. There have been billions of high quality photos
of the silicate sphere taken. (This is both literally true and a gross
underestimate.) How can the photo be fake if it better reflects what
the photographer saw than what can be deduced from only the raw pixels
of the sensor?
Of course, this example differs only in degree from common practice
going back to the beginning of photography. Photos have always been
modified, sometimes in order to deceive the viewer, but most often to
make the photos more like what the photographer believed the scene
actually looked like. For example, in nearly every photo I take I
"correct" the color balance.
Is the photo with a detailed Moon fake? Are my photos taken at the
forest floor, but without everything being some shade of green, fake? I
think most people would be satisfied if there was a way for them to know
what sources of information were used in creating the image.
We, as scientists, are much more demanding of our PDB models. We
build better models when we use all the knowledge at our disposal. If
we are interpreting a 9A resolution map of hemoglobin and see a
disk-shaped piece of density where we know the heme goes, we are
perfectly justified to build an atomic model of heme. We are also
obliged to make clear that the exact atomic positions, bond lengths and
angles, were not derived from that map, just as a journalist needs to
make clear to the reader that their photo has been processed to include
detail which was not present when the image was "taken".
I have deposited models that contained features which were only
"consistent" with the electron density but supported by enough other
forms of evidence to make me confident in their existence. I have done
my best to make the justification of these models clear in the reports I
have written but continue to be frustrated by the lack of tools to
represent the precise interplay of data sources that support my model
WITHIN the deposition. I am not so naive to believe that everyone who
has cited my papers have actually read them.
Dale E. Tronrud
On 3/10/2023 1:05 AM, Julia Griese wrote:
Hi all,
My impression has been that the most common approach these days is to
“let the B-factors take care of it”, but I might be wrong. Maybe it’s
time to run another poll?
Personally, I call any other approach R-factor cosmetics. The goal in
model building is not to achieve the lowest possible R-factors, it’s to
build the most physically meaningful, most likely to be correct, model.
So if you know that the side chain is part of the protein, you should
model it the best way you can. If it’s there, just disordered, then the
most correct way to model it is to let it have high B-factors. Most
molecular graphics programs don’t flag zero-occupancy atoms, so the user
might never notice. Truncation of a side chain, unless there is evidence
that it really physically isn’t there, is also misleading, in my
opinion. I don’t believe that it is more helpful to the non-expert user
than high B-factors either.
If people who are not structural biologists themselves don’t know how to
use a structure, then we need to educate them better. It is very
straightforward these days to look at electron density in the PDB
viewer. It used to be difficult, but nowadays there’s no excuse for not
checking the electron density. The PDB validation flags RSRZ outliers.
You can easily colour a structure by B-factors. It doesn’t take that
much effort to teach students how to validate structures. The main point
you need to get across is that it is necessary to do so. And this needs
to be done not only in courses aimed at prospective experimental
structural biologists, of course, but whenever students use structures
in any way.
This is just the opinion of someone who feels very strongly about
teaching structure validation and rejoices when students’ reply to the
question “What was the most important thing you learned today?” is:
“Don’t blindly trust anything.”
Cheers
/Julia
--
Dr. Julia Griese
Associate Professor (Docent)
Principal Investigator
Department of Cell and Molecular Biology
Uppsala University
BMC, Box 596
SE-75124 Uppsala
Sweden
email: julia.gri...@icm.uu.se
phone: +46-(0)18-471 4982
http://www.icm.uu.se/structural-biology/griese-lab/
<http://www.icm.uu.se/structural-biology/griese-lab/>
*From: *CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> on behalf of
Bernhard Lechtenberg <0000968307750321-dmarc-requ...@jiscmail.ac.uk>
*Reply-To: *Bernhard Lechtenberg <lechtenber...@wehi.edu.au>
*Date: *Friday, March 10, 2023 at 05:07
*To: *"CCP4BB@JISCMAIL.AC.UK" <CCP4BB@JISCMAIL.AC.UK>
*Subject: *Re: [ccp4bb] To Trim or Not to To Trim
I found the poll I wrote about earlier. This actually is way older than
I had expected (2011). You can see the poll results (which was run by Ed
Pozharski) and discussion at the time here in the CCP4BB archive:
https://www.mail-archive.com/ccp4bb@jiscmail.ac.uk/msg20268.html
<https://www.mail-archive.com/ccp4bb@jiscmail.ac.uk/msg20268.html>
In brief, the results of 240 respondents were:
Delete the atoms 43%
Let refinement take care of it by inflating B-factors 41%
Set occupancy to zero 12%
Other 4%
Bernhard
*From: *CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> on behalf of Debanu
Das <debanu....@gmail.com>
*Date: *Friday, 10 March 2023 at 2:56 pm
*To: *CCP4BB@JISCMAIL.AC.UK <CCP4BB@JISCMAIL.AC.UK>
*Subject: *Re: [ccp4bb] To Trim or Not to To Trim
We dealt with this in-depth during structural genomics days when we
deposited over 1500 novel, high-quality, experimentally-phased
structures into the PDB. Think it’s prudent to trim/truncate side chains
without reliable density.
Non-structural biologists using PDB structures without expert help can
err in any of these scenarios: misinterpreting most common/random
rotamer, zero occupancy atoms, B-factors, etc.
What is the value of populating the PDB, which is a structural model
repository, with such information that is not there, i.e., reliable
structural model?
Any trained crystallographer/structural biologist can easily add in side
chain information if needed for modeling/computational chemistry reasons.
Best regards,
Debanu
On Thu, Mar 9, 2023 at 6:50 PM Jurgen Bosch <jxb...@case.edu
<mailto:jxb...@case.edu>> wrote:
I’d say no trimming to side chains for the following reason: There
are non-structural biologists using PDB files and if atoms are
missing they don’t know what to do. A better approach is where no
side chain density allows support of placement, pick the most common
rotamer and set the occupancy to zero for those atoms lacking
density support. More work for you but more accurate in my opinion.
Jürgen
_______________________________________________
Jürgen Bosch, PhD, MBA
Center for Global Health & Diseases
Case Western Reserve University
Cleveland, OH 44106
https://www.linkedin.com/in/jubosch/
<https://www.linkedin.com/in/jubosch/>
CEO & Co-Founder at InterRayBio, LLC
On Mar 9, 2023, at 9:45 PM, Bernhard Lechtenberg
<0000968307750321-dmarc-requ...@jiscmail.ac.uk
<mailto:0000968307750321-dmarc-requ...@jiscmail.ac.uk>> wrote:
Hi Rhys,
I am also all for leaving side chains and letting the B-factors
deal with the weak/absent density.
I don’t think there is a consensus, but I kind of remember that
somebody did a poll a few years ago and if I remember correctly
the main approaches were the one described above, or trimming
the side-chains.
Bernhard
*Bernhard C. Lechtenberg* PhD
NHMRC Emerging Leadership Fellow
Laboratory Head
Ubiquitin Signalling Division
E lechtenber...@wehi.edu.au <mailto:lechtenber...@wehi.edu.au>
T +61 3 9345 2217
*From: *CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK
<mailto:CCP4BB@JISCMAIL.AC.UK>> on behalf of Rhys Grinter
<000022087c81e8c6-dmarc-requ...@jiscmail.ac.uk
<mailto:000022087c81e8c6-dmarc-requ...@jiscmail.ac.uk>>
*Date: *Friday, 10 March 2023 at 12:26 pm
*To: *CCP4BB@JISCMAIL.AC.UK <mailto:CCP4BB@JISCMAIL.AC.UK>
<CCP4BB@JISCMAIL.AC.UK <mailto:CCP4BB@JISCMAIL.AC.UK>>
*Subject: *[ccp4bb] To Trim or Not to To Trim
Hi All,
I'm trying to crowdsource an opinion on how people deal with
modelling side chains with poorly resolved electron or cryoEM
density.
My preference is to model the sidechain and allow the B-factors
to go high in refinement to represent that the side chain is
flexible. However, I'm aware that some people truncate
sidechains if density is not present to justify modelling. I've
also seen models where the sidechain is modelled but with zero
occupancy if density isn't present.
Is there a consensus and justifying arguments for why one
approach is better?
Cheers,
Rhys
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LinkedIn: www.linkedin.com/in/debanudas
<http://www.linkedin.com/in/debanudas>
Cal Alumni: cal.berkeley.edu/debanudas <http://cal.berkeley.edu/debanudas>
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