Re: [ccp4bb] To Trim or Not to To Trim

[Tom Peat]

Gotta love the extra wood on the fire.
In the bad old days, I agree, we had no real idea.
But these days I usually have mass spec done on most everything and 
additionally look at different crystal forms. Often I find that in one space 
group more will be seen than in another (and that one isn't necessarily the 
highest resolution) and these are even often from the same plate/ screen. 
Additionally, many proteins form oligomers or are found in multiple copies in 
the asymmetric unit, and these again vary as to how much of that mystical 
N-terminus or C-terminus one sees. I would be pretty confident that it isn't 
just one protomer in a trimer/ tetramer that has that extension and the rest of 
have selectively proteolysed...
Good point though. cheers, tom

From: CCP4 bulletin board  on behalf of Jurgen Bosch 

Sent: Saturday, March 11, 2023 8:37 AM
To: CCP4BB@JISCMAIL.AC.UK 
Subject: Re: [ccp4bb] To Trim or Not to To Trim

You don't often get email from jxb...@case.edu. Learn why this is 
important
Well Tom,

Your missing N-terminus might just be degraded same with the C-terminus two do 
you know it is actually there waving at you? Do you have mass spec evidence for 
the full existence of your protein? You might just have crystalized that 
magical fragment thinking that your full length construct is actually 
crystallized.

Just throwing some wood into the fire …

Jürgen

On Mar 10, 2023, at 4:01 PM, Debanu Das  wrote:

Hi Tom,

-"so no matter how much we try to educate people, the vast (vast, vast) 
majority of people will take the models as the 'truth'
-"So if we don't see something, the conservative approach is to probably avoid 
putting it in, otherwise it will get propagated forever"

I absolutely agree. I have a recent anecdote about this to share. I was at a 
workshop where the majority of attendees were medicinal chemists, comp 
chemists, biologists. I found out that some (many?) were even performing comp 
chem studies (where ligands and waters were important) on structures downloaded 
straight from the PDB without even checking associated electron density for 
such ligands/waters or even realizing potential side chain issues (not even 
including about any potential main chain or other quality/validation issues).

Best regards,
Debanu
--
Debanu Das,
https://bio.site/debanu_das

On Fri, Mar 10, 2023 at 12:41 PM Tom Peat 
mailto:t.p...@unsw.edu.au>> wrote:
Hello All,

I agree with Dale that we don't have a good way to model these things and it 
has been a discussion for a very long time with no proper answer.

Two more small points- we (or at least I do this all the time) don't model the 
N- or C-terminal residues that I don't see. They are most likely there 
somewhere (waving goodbye in the solvent mask) and that seems to be 
(relatively) standard practice, so I'm not sure how different this is to not 
putting in side chains that can't be seen? We don't replace with Ala, so people 
should know what the actual sequence is, but there is no evidence for a side 
chain. A multi-model is likely the better way to go, but isn't as feasible 
currently as the single model we normally deposit. As mentioned by others, we 
shouldn't try to put in ligands or co-factors that we don't see either...

One other point- although we should educate, the PDB has estimated that 99% of 
the users are not structural biologists (nor modellers or others with 
training), so no matter how much we try to educate people, the vast (vast, 
vast) majority of people will take the models as the 'truth'. So if we don't 
see something, the conservative approach is to probably avoid putting it in, 
otherwise it will get propagated forever.

My two cents. cheers, tom

From: CCP4 bulletin board mailto:CCP4BB@JISCMAIL.AC.UK>> 
on behalf of Dale Tronrud mailto:de...@daletronrud.com>>
Sent: Saturday, March 11, 2023 7:15 AM
To: CCP4BB@JISCMAIL.AC.UK 
mailto:CCP4BB@JISCMAIL.AC.UK>>
Subject: Re: [ccp4bb] To Trim or Not to To Trim

Hi

As a frequent contributor to prior discussions on this same topic I
would like to broaden the discussion a bit.  I'm sorry to say that most
of the comments on this threat are exactly the same positions that have
been expressed many times over the years.  I don't want to spent time,
again, retyping my opinions on how I prefer to torment the parameters of
my models to express what I believe is going on inside my crystals.

The fundamental problem is that the parameters we are forced to use,
in our PDB depositions and in the refinement and model building programs
available to us, are wholly inadequate.  We cannot accurately (or
precisely) describe what we are are envisioning for the surface side
chains, and sometimes entire stretches of main chain, in our proteins.
We can continue to argue with each other year after year, but there is
no solution to this problem other than 

Re: [ccp4bb] To Trim or Not to To Trim

[Quyen Hoang]

Hi Debanu,In your example, I would guess that models with truncated side chains would probably be problematic too, so would alternative conformations, unmodelled segments, asymmetric unit consisting of only a fraction of the biological/functional unit, etc.I am not sure if it is possible to build a model in a way that would avoid all the potential pitfalls in the circumstance you mentioned. Or should one even try?I don't remember ever solving a structure for the purpose of providing a model for computational chemists to use. We solve structures to answer certain questions and I would rather deposit the models we used to gain the insight we seeked instead of the one artificially made in the attempt to avoid misuses or understanding by non-structural biologists. Cheers,QuyenOn Mar 10, 2023, at 4:01 PM, Debanu Das  wrote:Hi Tom,-"so no matter how much we try to educate people, the vast (vast, vast) majority of people will take
 the models as the 'truth'-"So if we don't see something, the conservative approach is to probably 
avoid putting it in, otherwise it will get propagated forever"I absolutely agree. I have a recent anecdote about this to share. I was at a workshop where the majority of attendees were medicinal chemists, comp chemists, biologists. I found out that some (many?) were even performing comp chem studies (where ligands and waters were important) on structures downloaded straight from the PDB without even checking associated electron density for such ligands/waters or even realizing potential side chain issues (not even including about any potential main chain or other quality/validation issues).   Best regards,Debanu--Debanu Das,https://bio.site/debanu_dasOn Fri, Mar 10, 2023 at 12:41 PM Tom Peat  wrote:






Hello All, 




I agree with Dale that we don't have a good way to model these things and it has been a discussion for a very long time with no proper answer. 




Two more small points- we (or at least I do this all the time) don't model the N- or C-terminal residues that I don't see. They are most likely there somewhere (waving goodbye in the solvent mask) and that seems to be (relatively) standard practice, so I'm
 not sure how different this is to not putting in side chains that can't be seen? We don't replace with Ala, so people should know what the actual sequence is, but there is no evidence for a side chain. A multi-model is likely the better way to go, but isn't
 as feasible currently as the single model we normally deposit. As mentioned by others, we shouldn't try to put in ligands or co-factors that we don't see either... 




One other point- although we should educate, the PDB has estimated that 99% of the users are not structural biologists (nor modellers or others with training), so no matter how much we try to educate people, the vast (vast, vast) majority of people will take
 the models as the 'truth'. So if we don't see something, the conservative approach is to probably avoid putting it in, otherwise it will get propagated forever. 




My two cents. cheers, tom 


From: CCP4 bulletin board  on behalf of Dale Tronrud 
Sent: Saturday, March 11, 2023 7:15 AM
To: CCP4BB@JISCMAIL.AC.UK 
Subject: Re: [ccp4bb] To Trim or Not to To Trim
 


Hi

    As a frequent contributor to prior discussions on this same topic I 
would like to broaden the discussion a bit.  I'm sorry to say that most 
of the comments on this threat are exactly the same positions that have 
been expressed many times over the years.  I don't want to spent time, 
again, retyping my opinions on how I prefer to torment the parameters of 
my models to express what I believe is going on inside my crystals.

    The fundamental problem is that the parameters we are forced to use, 
in our PDB depositions and in the refinement and model building programs 
available to us, are wholly inadequate.  We cannot accurately (or 
precisely) describe what we are are envisioning for the surface side 
chains, and sometimes entire stretches of main chain, in our proteins. 
We can continue to argue with each other year after year, but there is 
no solution to this problem other than changing the nature of PDB models 
and allowing a reasonable description of multi-conformation models.

    I believe it is fair to say that the consensus after a previous 
round of this discussion was that, at the very least, we need a flag for 
each atom which indicates whether that atom was placed based on electron 
density or simply to make a chemically complete set of atoms for that 
type of monomer.  I haven't looked but I think that was about five or 
ten years ago.  Since then the PDB has made major changes to the 
structure of PDB entries that will require most software for analysis of 
macromolecular models be rewritten and right now that organization is 
making a major push to get us to virtually attend a workshop to help us 
make this transition.  

Re: [ccp4bb] To Trim or Not to To Trim

[CCP4BB]

On thus topic, I note that the "ModelCIF" format has been developed which 
allows inclusion of appropriate parameters associated with predicted models, 
such as those from AlphaFold (e.g. confidence values instead of B-values).  

Would it be too much to ask for fields associated with "modelled but not seen" 
parts of a model to be included in this expanded format (or even in the normal 
PDBx/mmcif dictionary)?

Harry
--
Dr Harry Powell

> On 10 Mar 2023, at 20:15, Dale Tronrud  wrote:
> 
> Hi
> 
>   As a frequent contributor to prior discussions on this same topic I would 
> like to broaden the discussion a bit.  I'm sorry to say that most of the 
> comments on this threat are exactly the same positions that have been 
> expressed many times over the years.  I don't want to spent time, again, 
> retyping my opinions on how I prefer to torment the parameters of my models 
> to express what I believe is going on inside my crystals.
> 
>   The fundamental problem is that the parameters we are forced to use, in our 
> PDB depositions and in the refinement and model building programs available 
> to us, are wholly inadequate.  We cannot accurately (or precisely) describe 
> what we are are envisioning for the surface side chains, and sometimes entire 
> stretches of main chain, in our proteins. We can continue to argue with each 
> other year after year, but there is no solution to this problem other than 
> changing the nature of PDB models and allowing a reasonable description of 
> multi-conformation models.
> 
>   I believe it is fair to say that the consensus after a previous round of 
> this discussion was that, at the very least, we need a flag for each atom 
> which indicates whether that atom was placed based on electron density or 
> simply to make a chemically complete set of atoms for that type of monomer.  
> I haven't looked but I think that was about five or ten years ago.  Since 
> then the PDB has made major changes to the structure of PDB entries that will 
> require most software for analysis of macromolecular models be rewritten and 
> right now that organization is making a major push to get us to virtually 
> attend a workshop to help us make this transition.  And yet I don't think 
> there is anything in this new data dictionary to help us with this important 
> but intractable problem.
> 
>   Unless the PDB gives us the parameters we need to properly describe a 
> macromolecular model, and the refinement/model building developers give us 
> the tools to make use of them, we will be back here again, every five years 
> or so, rehashing this debate over exactly the same, irreconcilably poor, 
> solutions to this problem.
> 
> 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 

Re: [ccp4bb] To Trim or Not to To Trim

[Tom Peat]

Hello All,

I agree with Dale that we don't have a good way to model these things and it 
has been a discussion for a very long time with no proper answer.

Two more small points- we (or at least I do this all the time) don't model the 
N- or C-terminal residues that I don't see. They are most likely there 
somewhere (waving goodbye in the solvent mask) and that seems to be 
(relatively) standard practice, so I'm not sure how different this is to not 
putting in side chains that can't be seen? We don't replace with Ala, so people 
should know what the actual sequence is, but there is no evidence for a side 
chain. A multi-model is likely the better way to go, but isn't as feasible 
currently as the single model we normally deposit. As mentioned by others, we 
shouldn't try to put in ligands or co-factors that we don't see either...

One other point- although we should educate, the PDB has estimated that 99% of 
the users are not structural biologists (nor modellers or others with 
training), so no matter how much we try to educate people, the vast (vast, 
vast) majority of people will take the models as the 'truth'. So if we don't 
see something, the conservative approach is to probably avoid putting it in, 
otherwise it will get propagated forever.

My two cents. cheers, tom

From: CCP4 bulletin board  on behalf of Dale Tronrud 

Sent: Saturday, March 11, 2023 7:15 AM
To: CCP4BB@JISCMAIL.AC.UK 
Subject: Re: [ccp4bb] To Trim or Not to To Trim

Hi

As a frequent contributor to prior discussions on this same topic I
would like to broaden the discussion a bit.  I'm sorry to say that most
of the comments on this threat are exactly the same positions that have
been expressed many times over the years.  I don't want to spent time,
again, retyping my opinions on how I prefer to torment the parameters of
my models to express what I believe is going on inside my crystals.

The fundamental problem is that the parameters we are forced to use,
in our PDB depositions and in the refinement and model building programs
available to us, are wholly inadequate.  We cannot accurately (or
precisely) describe what we are are envisioning for the surface side
chains, and sometimes entire stretches of main chain, in our proteins.
We can continue to argue with each other year after year, but there is
no solution to this problem other than changing the nature of PDB models
and allowing a reasonable description of multi-conformation models.

I believe it is fair to say that the consensus after a previous
round of this discussion was that, at the very least, we need a flag for
each atom which indicates whether that atom was placed based on electron
density or simply to make a chemically complete set of atoms for that
type of monomer.  I haven't looked but I think that was about five or
ten years ago.  Since then the PDB has made major changes to the
structure of PDB entries that will require most software for analysis of
macromolecular models be rewritten and right now that organization is
making a major push to get us to virtually attend a workshop to help us
make this transition.  And yet I don't think there is anything in this
new data dictionary to help us with this important but intractable
problem.

Unless the PDB gives us the parameters we need to properly describe
a macromolecular model, and the refinement/model building developers
give us the tools to make use of them, we will be back here again, every
five years or so, rehashing this debate over exactly the same,
irreconcilably poor, solutions to this problem.

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 

Re: [ccp4bb] To Trim or Not to To Trim

[Dale Tronrud]

Hi

   As a frequent contributor to prior discussions on this same topic I 
would like to broaden the discussion a bit.  I'm sorry to say that most 
of the comments on this threat are exactly the same positions that have 
been expressed many times over the years.  I don't want to spent time, 
again, retyping my opinions on how I prefer to torment the parameters of 
my models to express what I believe is going on inside my crystals.


   The fundamental problem is that the parameters we are forced to use, 
in our PDB depositions and in the refinement and model building programs 
available to us, are wholly inadequate.  We cannot accurately (or 
precisely) describe what we are are envisioning for the surface side 
chains, and sometimes entire stretches of main chain, in our proteins. 
We can continue to argue with each other year after year, but there is 
no solution to this problem other than changing the nature of PDB models 
and allowing a reasonable description of multi-conformation models.


   I believe it is fair to say that the consensus after a previous 
round of this discussion was that, at the very least, we need a flag for 
each atom which indicates whether that atom was placed based on electron 
density or simply to make a chemically complete set of atoms for that 
type of monomer.  I haven't looked but I think that was about five or 
ten years ago.  Since then the PDB has made major changes to the 
structure of PDB entries that will require most software for analysis of 
macromolecular models be rewritten and right now that organization is 
making a major push to get us to virtually attend a workshop to help us 
make this transition.  And yet I don't think there is anything in this 
new data dictionary to help us with this important but intractable 
problem.


   Unless the PDB gives us the parameters we need to properly describe 
a macromolecular model, and the refinement/model building developers 
give us the tools to make use of them, we will be back here again, every 
five years or so, rehashing this debate over exactly the same, 
irreconcilably poor, solutions to this problem.


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/ 



*From: *CCP4 bulletin board  on behalf of 
Bernhard Lechtenberg <968307750321-dmarc-requ...@jiscmail.ac.uk>

*Reply-To: *Bernhard Lechtenberg 
*Date: *Friday, March 10, 2023 at 05:07
*To: *"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 

Re: [ccp4bb] To Trim or Not to To Trim

[Julia Griese]

Hi Phil,

I don't think that this is model cosmetics, but I certainly didn't claim that 
this isn't controversial. That's why we're having this discussion again and 
again after all.

Have you tried to model a disordered Arg with 10 (why only 10?) alternate 
rotamers? Did it refine to something sensible? If so, then I would agree that 
this would be better. I haven't tried it, but I suspect they would all converge 
more or less on top of each other. (If anyone wants to give it a try, please 
let me know what happened!)

I still maintain that modeling a disordered Arg as an Arg with a single rotamer 
with high B-factors is more correct than modeling it as an Ala or setting its 
side chain occupancy to zero, because it is not an Ala, and its side chain 
atoms are not absent. (Yes, I see Harry's point, but let's assume you've 
collected your data carefully and don't have such serious radiation damage that 
you've lost arginine side chains. If that was the case, you'd be missing a 
whole lot of other side chains too.) I do not claim that such a model 
accurately reflects where the Arg really is, I only claim that it's the best we 
can do (at present). Hence why we need to educate users.

And absolutely, none of the current solutions is ideal, that's also why we're 
having this discussion again and again. It seems no one has found a better 
solution yet.

/Julia

On 3/10/23, 17:15, "Phil Jeffrey" mailto:pjeff...@princeton.edu>> wrote:


On 3/10/23 4:05 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.


And I could call your approach "model cosmetics".


If you can't see the side-chain, you don't know where it is and you
probably don't even know where the centroid of the distribution is.
Only in the case of very short side-chains with few rotamers can you
make a reasonable volume approximation to where the side-chain is and
"let the B-factors" smear out the density to cover a range of the
projected conformations.


For longer side-chains, if you put it in a single conformation, you are
very likely NOT coming close to correctly modeling the actual
distribution of the conformations. So let's circle back on "most likely
to be correct model" and ask what we *actually* know about where the
atoms are.


Put your disordered Arg in with 10 alternate conformations, each with a
refined relative occupancy, and then let the B-factors smear that lot
out, and that's your better model.


Phil Jeffrey
Princeton






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Re: [ccp4bb] To Trim or Not to To Trim

[Julia Griese]

Surely not if the locations of those other atoms are strongly supported by 
density? And surely you would always select a rotamer that does not clash with 
its surroundings?

On 3/10/23, 17:32, "CCP4 bulletin board on behalf of Goldman, Adrian" 
mailto:CCP4BB@JISCMAIL.AC.UK> on behalf of 
adrian.gold...@helsinki.fi > wrote:


Maybe simplest just to trim it back. I do worry that the presence of a wrong 
conformation will lead to inaccurate vdw clashes that could negatively affect 
other atoms.


Sent from my iPhone


> On 10 Mar 2023, at 18:25, Phil Jeffrey  > wrote:
>
> On 3/10/23 4:05 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.
>
> And I could call your approach "model cosmetics".
>
> If you can't see the side-chain, you don't know where it is and you probably 
> don't even know where the centroid of the distribution is. Only in the case 
> of very short side-chains with few rotamers can you make a reasonable volume 
> approximation to where the side-chain is and "let the B-factors" smear out 
> the density to cover a range of the projected conformations.
>
> For longer side-chains, if you put it in a single conformation, you are very 
> likely NOT coming close to correctly modeling the actual distribution of the 
> conformations. So let's circle back on "most likely to be correct model" and 
> ask what we *actually* know about where the atoms are.
>
> Put your disordered Arg in with 10 alternate conformations, each with a 
> refined relative occupancy, and then let the B-factors smear that lot out, 
> and that's your better model.
>
> Phil Jeffrey
> Princeton
>
> 
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Re: [ccp4bb] To Trim or Not to To Trim

[Quyen Hoang]

As with Jurgen, I’ve never trimmed a residue.
In my view the trimmed residues do not exist.
If we were to build models consisting of only atoms defined by the experimental 
density, then I wonder what the original model of the DNA double helix would 
have looked like.

BTW, hey Jurgen, long time no talk.

Cheers,
Quyen

Quyen Hoang, PhD
Professor of Biochemistry and Molecular Biology
Director of IUSM Center for Electron Microscopy (iCEM)
Adjunct Professor of Neurology
Primary Investigator of the Stark Neuroscience Research Institute
Indiana University School of Medicine
635 Barnhill Drive, MS0013C
Indianapolis, IN, 46202
(317)274-4371
https://qqhoang.pages.iu.edu


> On Mar 10, 2023, at 12:09 PM, Jurgen Bosch  wrote:
> 
> I’m sure James H. Is preparing a philosophical dissertation on the "State of 
> the atoms to B or not to B that is not only a refinement question” that he 
> will share momentarily with the board.
> 
> Jürgen 
> 
>> On Mar 10, 2023, at 12:06 PM, DEBANU DAS  
>> wrote:
>> 
>> Yes, zero occupancy would reflect that. But not the coordinates in any 
>> proper way. 
>> Debanu
>> 
>> On Fri, Mar 10, 2023 at 8:58 AM Jurgen Bosch > > wrote:
>> Going back to RIP phasing methods :-)
>> So Harry in your particular case occupancy of zero would actually reflect 
>> reality for those “combusted” atoms.
>> 
>> Jürgen 
>> 
>> > On Mar 10, 2023, at 11:56 AM, Harry Powell 
>> > <193323b1e616-dmarc-requ...@jiscmail.ac.uk 
>> > > wrote:
>> > 
>> > Hi folks
>> > 
>> > One other thing that I haven’t noticed anyone mentioning yet (sorry to 
>> > those who have mentioned it!!) is that you may not see your sidechain 
>> > atoms in density because they are not there at all, in spite of what you 
>> > may have had in the original protein, or even if the atoms were really 
>> > there in the crystal _before_ exposure to the beam.
>> > 
>> > The coordinates are supposed to be what you actually find, not what you 
>> > hope is there.
>> > 
>> > Just my two ha’porth
>> > 
>> > Harry
>> > 
>> > 
>> > 
>> > To unsubscribe from the CCP4BB list, click the following link:
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>> > 
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Re: [ccp4bb] To Trim or Not to To Trim

[Jurgen Bosch]

I’m sure James H. Is preparing a philosophical dissertation on the "State of 
the atoms to B or not to B that is not only a refinement question” that he will 
share momentarily with the board.

Jürgen 

> On Mar 10, 2023, at 12:06 PM, DEBANU DAS  
> wrote:
> 
> Yes, zero occupancy would reflect that. But not the coordinates in any proper 
> way. 
> Debanu
> 
> On Fri, Mar 10, 2023 at 8:58 AM Jurgen Bosch  > wrote:
>> Going back to RIP phasing methods :-)
>> So Harry in your particular case occupancy of zero would actually reflect 
>> reality for those “combusted” atoms.
>> 
>> Jürgen 
>> 
>> > On Mar 10, 2023, at 11:56 AM, Harry Powell 
>> > <193323b1e616-dmarc-requ...@jiscmail.ac.uk 
>> > > wrote:
>> > 
>> > Hi folks
>> > 
>> > One other thing that I haven’t noticed anyone mentioning yet (sorry to 
>> > those who have mentioned it!!) is that you may not see your sidechain 
>> > atoms in density because they are not there at all, in spite of what you 
>> > may have had in the original protein, or even if the atoms were really 
>> > there in the crystal _before_ exposure to the beam.
>> > 
>> > The coordinates are supposed to be what you actually find, not what you 
>> > hope is there.
>> > 
>> > Just my two ha’porth
>> > 
>> > Harry
>> > 
>> > 
>> > 
>> > To unsubscribe from the CCP4BB list, click the following link:
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Re: [ccp4bb] To Trim or Not to To Trim

[Harry Powell]

Hi Jürgen

You might think so, but I’d disagree. Not going too far away from your line of 
reasoning I could also put in a completely fictitious ligand or cofactor and 
assign its occupancies to zero (I really, really knew it was there but I just 
couldn’t find any evidence… :-))

Harry

> On 10 Mar 2023, at 16:58, Jurgen Bosch  wrote:
> 
> Going back to RIP phasing methods :-)
> So Harry in your particular case occupancy of zero would actually reflect 
> reality for those “combusted” atoms.
> 
> Jürgen 
> 
>> On Mar 10, 2023, at 11:56 AM, Harry Powell 
>> <193323b1e616-dmarc-requ...@jiscmail.ac.uk> wrote:
>> 
>> Hi folks
>> 
>> One other thing that I haven’t noticed anyone mentioning yet (sorry to those 
>> who have mentioned it!!) is that you may not see your sidechain atoms in 
>> density because they are not there at all, in spite of what you may have had 
>> in the original protein, or even if the atoms were really there in the 
>> crystal _before_ exposure to the beam.
>> 
>> The coordinates are supposed to be what you actually find, not what you hope 
>> is there.
>> 
>> Just my two ha’porth
>> 
>> Harry
>> 
>> 
>> 
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Re: [ccp4bb] To Trim or Not to To Trim

[Debanu Das]

Yes, zero occupancy would reflect that. But not the coordinates in any
proper way. Then what would be the point of associating occupancy and
B-factors with totally incorrect coordinates?
Debanu

On Fri, Mar 10, 2023 at 8:58 AM Jurgen Bosch  wrote:

> Going back to RIP phasing methods :-)
> So Harry in your particular case occupancy of zero would actually reflect
> reality for those “combusted” atoms.
>
> Jürgen
>
> > On Mar 10, 2023, at 11:56 AM, Harry Powell <
> 193323b1e616-dmarc-requ...@jiscmail.ac.uk> wrote:
> >
> > Hi folks
> >
> > One other thing that I haven’t noticed anyone mentioning yet (sorry to
> those who have mentioned it!!) is that you may not see your sidechain atoms
> in density because they are not there at all, in spite of what you may have
> had in the original protein, or even if the atoms were really there in the
> crystal _before_ exposure to the beam.
> >
> > The coordinates are supposed to be what you actually find, not what you
> hope is there.
> >
> > Just my two ha’porth
> >
> > Harry
> >
> > 
> >
> > To unsubscribe from the CCP4BB list, click the following link:
> > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1
> >
> > This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a
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Re: [ccp4bb] To Trim or Not to To Trim

[Jurgen Bosch]

Going back to RIP phasing methods :-)
So Harry in your particular case occupancy of zero would actually reflect 
reality for those “combusted” atoms.

Jürgen 

> On Mar 10, 2023, at 11:56 AM, Harry Powell 
> <193323b1e616-dmarc-requ...@jiscmail.ac.uk> wrote:
> 
> Hi folks
> 
> One other thing that I haven’t noticed anyone mentioning yet (sorry to those 
> who have mentioned it!!) is that you may not see your sidechain atoms in 
> density because they are not there at all, in spite of what you may have had 
> in the original protein, or even if the atoms were really there in the 
> crystal _before_ exposure to the beam.
> 
> The coordinates are supposed to be what you actually find, not what you hope 
> is there.
> 
> Just my two ha’porth
> 
> Harry
> 
> 
> 
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Re: [ccp4bb] To Trim or Not to To Trim

[Harry Powell]

Hi folks

One other thing that I haven’t noticed anyone mentioning yet (sorry to those 
who have mentioned it!!) is that you may not see your sidechain atoms in 
density because they are not there at all, in spite of what you may have had in 
the original protein, or even if the atoms were really there in the crystal 
_before_ exposure to the beam.

The coordinates are supposed to be what you actually find, not what you hope is 
there.

Just my two ha’porth

Harry



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Re: [ccp4bb] To Trim or Not to To Trim

[Jon Agirre]

Are downstream users of models with poorly resolved regions more likely to
spot them if they have huge B-factors or zero occupancy? If the answer is
'neither', then perhaps we need to develop a different solution.

On Fri, 10 Mar 2023 at 16:33, Goldman, Adrian 
wrote:

> Maybe simplest just to trim it back. I do worry that the presence of a
> wrong conformation will lead to inaccurate vdw clashes that could
> negatively affect other atoms.
>
> Sent from my iPhone
>
> > On 10 Mar 2023, at 18:25, Phil Jeffrey  wrote:
> >
> > On 3/10/23 4:05 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.
> >
> > And I could call your approach "model cosmetics".
> >
> > If you can't see the side-chain, you don't know where it is and you
> probably don't even know where the centroid of the distribution is. Only in
> the case of very short side-chains with few rotamers can you make a
> reasonable volume approximation to where the side-chain is and "let the
> B-factors" smear out the density to cover a range of the projected
> conformations.
> >
> > For longer side-chains, if you put it in a single conformation, you are
> very likely NOT coming close to correctly modeling the actual distribution
> of the conformations.  So let's circle back on "most likely to be correct
> model" and ask what we *actually* know about where the atoms are.
> >
> > Put your disordered Arg in with 10 alternate conformations, each with a
> refined relative occupancy, and then let the B-factors smear that lot out,
> and that's your better model.
> >
> > Phil Jeffrey
> > Princeton
> >
> > 
> >
> > To unsubscribe from the CCP4BB list, click the following link:
> > https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB=1
> >
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-- 
Dr Jon Agirre [image: A button with "Hear my name" text for name playback
in email signature]  
Royal Society University Research Fellow
CCP4 WG2 co-chair and ED champion | instruct-ERIC representative @
3D-Bioinfo (Elixir)
York Structural Biology Laboratory, Department of Chemistry
University of York, Heslington, YO10 5DD, York, UK
http://www.york.ac.uk/chemistry/research/ysbl/people/staff/jagirre/
Office: /B/K/065 Phone: +44 (0) 1904 32 8252
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Re: [ccp4bb] To Trim or Not to To Trim

[Goldman, Adrian]

Maybe simplest just to trim it back. I do worry that the presence of a wrong 
conformation will lead to inaccurate vdw clashes that could negatively affect 
other atoms. 

Sent from my iPhone

> On 10 Mar 2023, at 18:25, Phil Jeffrey  wrote:
> 
> On 3/10/23 4:05 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. 
> 
> And I could call your approach "model cosmetics".
> 
> If you can't see the side-chain, you don't know where it is and you probably 
> don't even know where the centroid of the distribution is. Only in the case 
> of very short side-chains with few rotamers can you make a reasonable volume 
> approximation to where the side-chain is and "let the B-factors" smear out 
> the density to cover a range of the projected conformations.
> 
> For longer side-chains, if you put it in a single conformation, you are very 
> likely NOT coming close to correctly modeling the actual distribution of the 
> conformations.  So let's circle back on "most likely to be correct model" and 
> ask what we *actually* know about where the atoms are.
> 
> Put your disordered Arg in with 10 alternate conformations, each with a 
> refined relative occupancy, and then let the B-factors smear that lot out, 
> and that's your better model.
> 
> Phil Jeffrey
> Princeton
> 
> 
> 
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Re: [ccp4bb] To Trim or Not to To Trim

[Phil Jeffrey]

On 3/10/23 4:05 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. 


And I could call your approach "model cosmetics".

If you can't see the side-chain, you don't know where it is and you 
probably don't even know where the centroid of the distribution is. 
Only in the case of very short side-chains with few rotamers can you 
make a reasonable volume approximation to where the side-chain is and 
"let the B-factors" smear out the density to cover a range of the 
projected conformations.


For longer side-chains, if you put it in a single conformation, you are 
very likely NOT coming close to correctly modeling the actual 
distribution of the conformations.  So let's circle back on "most likely 
to be correct model" and ask what we *actually* know about where the 
atoms are.


Put your disordered Arg in with 10 alternate conformations, each with a 
refined relative occupancy, and then let the B-factors smear that lot 
out, and that's your better model.


Phil Jeffrey
Princeton



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Re: [ccp4bb] To Trim or Not to To Trim

[Rob Nicholls]

I believe Julia is absolutely right.

The other consideration that I haven’t seen mentioned yet in this thread is the 
effect on refinement. If you truncate a side chain or set it to zero occupancy 
then the bulk solvent mask would contain that region that is actually occupied 
by the flexible side chain in the crystal. The solvent mask is supposed to 
represent flat unordered solvent, and shouldn’t contain such ordered (though 
flexible) parts of the macromolecule. This is unavoidable in the case of larger 
unmodelled regions (e.g. missing surface loops, even whole domains at low 
resolution) and this hard problem is not accounted for using existing tools. 
But the simpler case of flexible/disordered side chains is something that we 
can do something to avoid: just build the side chain in and let the B-factors 
be accordingly inflated - those atoms must be approximately in that position in 
the crystal due to being restrained by covalent bonding, and the high B-factors 
will reflect the uncertainty/flexibility of the positioning.

And these days there are sufficient regularisers in use that the additional 
parameters from explicitly modelling the side chain shouldn’t be a problem, 
even at low resolution. Having more parameters *should* reduce Rwork if 
anything… although it will of course depend on refinement protocol/weights etc.

Zero occupancy atoms are not physically meaningful, and the fact that they are 
ignored during refinement means that the B-factors wouldn’t get refined and so 
wouldn’t reflect positional uncertainty, which could cause further issues with 
downstream misinterpretation. Similarly partial occupancies shouldn’t be used 
unless to specifically reflect the modelling assumption that those atoms are 
only physically present in a portion of the crystal.

Regards,
Rob



> On 10 Mar 2023, at 09:05, Julia Griese  wrote:
> 
> 
> CAUTION: This email originated from outside of the LMB.
> Do not click links or open attachments unless you recognize the sender and 
> know the content is safe.
> .-owner-ccp...@jiscmail.ac.uk -.
> 
> 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/ 
> 
>  
> From: CCP4 bulletin board  > on behalf of Bernhard Lechtenberg 
> <968307750321-dmarc-requ...@jiscmail.ac.uk 
> >
> Reply-To: Bernhard Lechtenberg  >
> Date: Friday, March 10, 2023 at 05:07
> To: "CCP4BB@JISCMAIL.AC.UK " 
> mailto:CCP4BB@JISCMAIL.AC.UK>>
> Subject: Re: [ccp4bb] To Trim or Not to To Trim
>  
> I found the poll I wrote about 

Re: [ccp4bb] To Trim or Not to To Trim

[Julia Griese]

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/

From: CCP4 bulletin board  on behalf of Bernhard 
Lechtenberg <968307750321-dmarc-requ...@jiscmail.ac.uk>
Reply-To: Bernhard Lechtenberg 
Date: Friday, March 10, 2023 at 05:07
To: "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

In brief, the results of 240 respondents were:
Delete the atoms 43%
Let refinement take care of it by inflating B-factors41%
Set occupancy to zero12%
Other 4%


Bernhard

From: CCP4 bulletin board  on behalf of Debanu Das 

Date: Friday, 10 March 2023 at 2:56 pm
To: 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 
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/

CEO & Co-Founder at InterRayBio, LLC



On Mar 9, 2023, at 9:45 PM, Bernhard Lechtenberg 
<968307750321-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 

Re: [ccp4bb] 9th CCP-EM Spring Symposium 25-27th April 2023

[Tom Burnley - STFC UKRI]

Dear all,

Final reminder that the early bird registration for the CCP-EM Symposium closes 
today (Friday 10th March).  After today the registration fees increase.

Registration link and more conference details here…

https://www.ccpem.ac.uk/training/spring_symposium_2023/spring_symposium_2023.php

* Bursaries applications - last call
We have a number of bursaries available thanks to our kind sponsors (Quantum 
Detectors, SPT Labtech & Quantifoil, Evotec, Dectris and Thermo Fisher 
Scientific ).  The bursaries can cover accommodation and registration for those 
who need them to attend in person.  Please submit any bursary requests by the 
end of today (Friday 10th March, see registration site for more details).  We 
will confirm bursary awards next week.

* Applying for a talk
As in previous years we are seeking a number of additional talks selected from 
submitted abstracts.
If interested, please submit a proposed title and abstract during registration 
for consideration by the scientific organisers or submit a talk title and 
abstract (up to 500 words) directly by email to:

ccpemeve...@stfc.ac.uk.

Please also include your name, position, group and institute.  We are 
particularly interested in abstracts with a computational focus e.g. new 
algorithms or methods for the spring symposium. For the BCI user meeting we 
welcome new results that have been made possible by use of eBIC in the last 
12-18 months.

* BCI User Survey
Please can all Diamond users of BCI facilities complete the survey by 11th 
April (see link below).  During the user meeting representatives from eBIC, B24 
and the Membrane Protein Lab (MPL) will discuss topics raised in the User 
Survey and welcome your feedback and support:

https://forms.office.com/pages/responsepage.aspx?id=dLonnQABDU2B_x1yja6N9k2iEV9rkoVBsESt7IZg17BUMk9XVzdDTUoyMTJERUg1N1JZUURFRzZKSy4u

All the best from CCP-EM & DLS BCI


From: Collaborative Computational Project in Electron cryo-Microscopy 
 on behalf of Tom Burnley - STFC UKRI 
<740061e4cf9b-dmarc-requ...@jiscmail.ac.uk>
Sent: 07 March 2023 14:15
To: cc...@jiscmail.ac.uk 
Subject: Re: [ccpem] 9th CCP-EM Spring Symposium 25-27th April 2023

Dear all,

Quick reminder that the early bird registration for the CCP-EM Symposium closes 
this Friday (10th March).  After that the registration fees increase.

Registration link and more conference details here…

https://www.ccpem.ac.uk/training/spring_symposium_2023/spring_symposium_2023.php

Also, we are close to selling out the available accommodation so if you are 
planning on coming in person please register soon.

Finally, we have a number of bursaries available thanks to our kind sponsors 
(Quantum Detectors, SPT Labtech & Quantifoil, Evotec and Thermo Fisher 
Scientific ).  The bursaries can cover accommodation and registration for those 
who need them to attend in person.  Please submit any bursary requests by 
Friday 10th March (see registration site for more details).  We will confirm 
bursary awards next week.

All the best from CCP-EM & DLS BCI


From: Burnley, Tom (STFC,RAL,SC)
Sent: 13 February 2023 13:57
To: ccpem mailing list ; ccpem mailing list 
; 3...@ncmir.ucsd.edu <3...@ncmir.ucsd.edu>
Subject: 9th CCP-EM Spring Symposium 25-27th April 2023

Dear CCP-EM,

We are pleased to announce the 9th Annual CCP-EM Spring Symposium. The 
conference aims to provide a forum to highlight state-of-the-art developments 
in computational cryoEM and related themes, as well as showcasing outstanding 
recent biological applications. We aim to promote an inclusive, friendly 
atmosphere, welcoming those both old and new to the community. Topics include 
instrument technology, sample preparation, image processing, single particle 
reconstruction, tomography and model building.

The meeting also includes the Diamond Light Source Biological Cryo-Imaging User 
Meeting for eBIC & B24 and two satellite meetings for SPT Labtech & eBIC for 
Industry.

The conference will be held as a hybrid meeting, with the physical event at the 
EMCC in Nottingham, plus virtual access online via Zoom. It is kindly sponsored 
by Quantum Detectors, SPT Labtech & Quantifoil, and Thermo Fisher Scientific.

Registration is open now:
https://cvent.me/5rk8kR

More details and schedule are available here:
https://www.ccpem.ac.uk/training/spring_symposium_2023/spring_symposium_2023.php

Confirmed Symposium speakers include:
Alan Brown (Harvard)
Beatriz Costa Gomes (Turing)
Tristan Croll (Altos)
Ieva Drulyte (TFS)
Rene Frank (Leeds)
Michael Grange (Franklin)
Matt Iadanza (STFC)
Kiarash Jamali (MRC-LMB)
Gerard Kleywegt (EBI)
Sam Lacey (Human Technopole)
Bonnie Murphy (Max Planck)
Randy Read (Cambridge)
Ricardo Righetto (Basel)
Elizabeth Villa (UCSD)* remote
Janet Vonck (Max Planck Biophysics)

Confirmed BCI speakers:
Bridget Carragher (Chan Zuckerberg Imaging Institute)
Victoria Garcia Giner (Imperial College London)
Peter Wing