Hello,

I think Rams’ last remark is very important. People with every preference 
regarding modelling (trimmed, zero-occupancy or high-B), past their 
disagreement on this particular question, are all concerned about how their 
models will be interpreted by non-experts.

Since all experimental scientists understand the difference between observed 
data and interpretation, I believe the best way to educate non-expert users of 
macromolecular models would be for the PDB to systematically show a map. An 
overview consisting of a still image with map and model is already in 
validation reports, so it could be displayed on the entry page on the web as 
well. We now have in-browser interactive map and model viewers, so the PDB 
should make use of this capability and show the map by default, and use a 
legend that would be clear for non-experts (with terms like "observed density" 
and "atomic model interpretation of the density" or whatever explains it best 
in easy words).

We could also all get into the habit of showing a map (or even only the region 
of interest in a map) in a main figure in our papers, instead of keeping it 
hidden deep in the supplementary figures. CryoEM papers often show a map in a 
main figure, and as a reader I think it is very nice to show me the map that 
convinced you of some finding before showing me your interpretation of this 
map. I hope the cryoEM field will keep doing this, and I hope the MX field 
would start showing more maps in their papers again. Think of a scatter plot 
analogy: what sense would it make to only show the fit line? and leave the data 
points in a supplementary figure or in some database fairly obscure for 
non-experts? This is what we are doing when we only show an atomic model. Then 
no wonder non-expert readers are confused.

Showing maps would go a long way to getting more people "structurally minded", 
until the root problem is fixed with better representations for macromolecular 
models (and viewer programs able to present all the info), like Dale suggested.

Cheers,

Guillaume


On 17 Mar 2023, at 12:25, Subramanian, Ramaswamy 
<[email protected]<mailto:[email protected]>> wrote:

Dear All,

I am kind of in agreement with Manfred, but I also have concerns.

The RCSB and the databases are public databases used by non-structural biology 
experts a lot.  They take the model as if it is an experimental result - rather 
than it being a model.

Example:  I just got a paper with reviewers' comments.   The reviewer insists 
that there is a crystal structure that clearly shows the conformation is XXX in 
the pdb and our interpretation of the biochemical data is wrong.  The B-factors 
of the atoms that he says contradict our results are over 100, and there is no 
density for them in the ED map.   I am writing with a justification, explaining 
all these - but I will see if it is accepted.  But the fact remains that this 
person who is an expert in a different field - still uses it and makes poor 
interpretations.

Are we doing a dis-service to the large group of non-experts, who think the 
positions are experimental results and interpret data?  They are often the 
audience for who we generate and deposit the data.

Thanks, and cheers!



Rams
[email protected]<mailto:[email protected]>



On Mar 17, 2023, at 4:57 AM, Manfred S. Weiss 
<[email protected]<mailto:[email protected]>> 
wrote:

---- External Email: Use caution with attachments, links, or sharing data ----


Dear all,

many views have been expressed in this thread, which I have been
following with great interest. Unfortunately, I have to say that many
of the views are more based on personal preferences, than on the
scientific evidence behind.

Here are some facts, that one may want to consider:

1. When you have crystallized your protein, and collected data
from it, the obvious assumption is that it is still intact. Unless you
have additional information, e.g. from mass spec, that some
side chains are cleaved off, they are there.

2. Absence of evidence (meaning missing electron density)
is NOT evidence of absence !!!!

3. If you trim, you give the impression that the respective atoms
are not there. This means that the solvent model will be incorrect,
because the area will be defined as solvent.

In my view, the best approach is to build the side chains in their
most plausible conformation, or maybe in 2 or 3 or 5 different
conformations, and let the ADPs refine freely.

All the best
Manfred




<http://www.icm.uu.se/structural-biology/griese-lab/>























































































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