Re: [ccp4bb] Meaning of a pdb entry

[Tim Gruene]

Dear Gergely,

you can concatenate (mm)CIF files, without violating the grammar. Thus,
if you want to deposit multiple models at once, just run 'cat 1.mmcif
2.mmcif 3.mmcif > allmy.mmcif' for deposition. This works for CIF, and
is accepted e.g. by the IUCR journals.

Best,
Tim

 On Mon, 31 May 2021
17:53:46 + Gergely Katona  wrote:

> Dear Ethan,
> 
> Thank you for your comments! I started a new thread, it was
> unfortunate that I brought this up in a discussion about B-factors. I
> really wanted to discuss something that is model agnostic and how to
> represent uncertainty by sampling. I consider an ensemble model with
> multiple partial occupancy molecules is still one model. 
> 
> I am not sure if it is possible to use MODEL-ENDMDL loops in pdb or
> mmcif format for storing multiple crystallographic models. I assume
> it is already possible to store multiple structure factor files (for
> refinement, for phasing, different crystals etc) under the same
> entry. In my mind, it would be a small step to associate different
> data sets distinguished by crystal ID or data block with a particular
> model number, but maybe it is not that simple. 
> 
> I do not want to create multiple pdb entries just to provide evidence
> for the robustness/reproducibility of crystals and crystallographic
> models. I would rather use different pdb entries for different
> sampling intentions: for example entry 1 contains all the control
> crystals, entry 2 contains all the crystals subjected to treatment A,
> etc. These would otherwise share identical data reduction and
> refinement protocols and most of the metadata. I am afraid I do know
> how the PDB and associated services work internally, but I hope
> someone here can provide guidance.
> 
> Best wishes,
> 
> Gergely
> 
> 
> Gergely Katona, Professor, Chairman of the Chemistry Program Council
> Department of Chemistry and Molecular Biology, University of
> Gothenburg Box 462, 40530 Göteborg, Sweden
> Tel: +46-31-786-3959 / M: +46-70-912-3309 / Fax: +46-31-786-3910
> Web: http://katonalab.eu, Email: gergely.kat...@gu.se
> 
> -Original Message-
> From: CCP4 bulletin board  On Behalf Of Ethan
> A Merritt Sent: 29 May, 2021 19:16
> To: CCP4BB@JISCMAIL.AC.UK
> Subject: Re: [ccp4bb] AW: [ccp4bb] AW: [ccp4bb] (R)MS
> 
> On Saturday, 29 May 2021 02:12:16 PDT Gergely Katona wrote:
> [...snip...]
>  I think the assumption of independent variations per atoms is too
> strong in many cases and does not give an accurate picture of
> uncertainty. [...snip...]
> 
> 
> Gergely, you are revisiting a line of thought that historically led
> to the introduction of more global treatments of atomic displacement.
> These have distinct statistical and interpretational advantages.
> 
> Several approaches have been tried over the past 40 years or so.
> The one that has proved most successful is the use of TLS
> (Translation/Libration/Screw) models of bulk displacement to
> supplement or replace per-atom descriptions.  As you say, a per-atom
> treatment is often too strong and is not statistically justified by
> the experimental data.  I explored this with specific examples in
> 
>"To B or not to B?" [Acta Cryst. 2012, D68, 468-477]
> http://skuld.bmsc.washington.edu/~tlsmd/references.html
> 
> An NMR-style approach that constructs and refines multiple discrete
> models has been been re-invented several times. These treatments are
> generally called "ensemble models".  IMHO they are statistically
> unjustified and strictly worse than treatments based on higher level
> descriptions such as TLS or normal-mode analysis. X-ray data is
> qualitatively different from NMR data, and optimal treatment of
> uncertainty must take this into account.
> 
>   best regards
> 
>   Ethan
> 
> 
> > Hi,
> > 
> > It is enough to have Ų as unit to express uncertainty in 3D, but
> > one can express it with a single number only in a very specific
> > case when the atom is isotropic. Few atoms have a naturally
> > isotropic distribution around their mean position in very high
> > resolution protein crystal structures. The anisotropic atoms can be
> > described by a 3x3 matrix, where each row and column is associated
> > with the uncertainty in a specific spatial direction. The matrix
> > elements are the product of the uncertainty in these directions.
> > The diagonal elements will be the square of uncertainty in the same
> > direction and they should be always positive, the off-diagonal
> > combination of directions are covariances (+,0 or -). In the end,
> > every element will have a unit distance*distance and the matrix
> > will be symmetric. We cannot just take the square root of the
> > matrix elements and expect something meaningful, if for no other
> > reason the problem with negative covariances. To calculate the
> > square root on the matrix itself one has to diagonalize it first.
> > The height of a person in your example  sounds easy to define, but
> > the mathematical formalism 

[ccp4bb] Meaning of a pdb entry

[Gergely Katona]

Dear Ethan,

Thank you for your comments! I started a new thread, it was unfortunate that I 
brought this up in a discussion about B-factors. I really wanted to discuss 
something that is model agnostic and how to represent uncertainty by sampling. 
I consider an ensemble model with multiple partial occupancy molecules is still 
one model. 

I am not sure if it is possible to use MODEL-ENDMDL loops in pdb or mmcif 
format for storing multiple crystallographic models. I assume it is already 
possible to store multiple structure factor files (for refinement, for phasing, 
different crystals etc) under the same entry. In my mind, it would be a small 
step to associate different data sets distinguished by crystal ID or data block 
with a particular model number, but maybe it is not that simple. 

I do not want to create multiple pdb entries just to provide evidence for the 
robustness/reproducibility of crystals and crystallographic models. I would 
rather use different pdb entries for different sampling intentions: for example 
entry 1 contains all the control crystals, entry 2 contains all the crystals 
subjected to treatment A, etc. These would otherwise share identical data 
reduction and refinement protocols and most of the metadata. I am afraid I do 
know how the PDB and associated services work internally, but I hope someone 
here can provide guidance.

Best wishes,

Gergely


Gergely Katona, Professor, Chairman of the Chemistry Program Council
Department of Chemistry and Molecular Biology, University of Gothenburg
Box 462, 40530 Göteborg, Sweden
Tel: +46-31-786-3959 / M: +46-70-912-3309 / Fax: +46-31-786-3910
Web: http://katonalab.eu, Email: gergely.kat...@gu.se

-Original Message-
From: CCP4 bulletin board  On Behalf Of Ethan A Merritt
Sent: 29 May, 2021 19:16
To: CCP4BB@JISCMAIL.AC.UK
Subject: Re: [ccp4bb] AW: [ccp4bb] AW: [ccp4bb] (R)MS

On Saturday, 29 May 2021 02:12:16 PDT Gergely Katona wrote:
[...snip...]
 I think the assumption of independent variations per atoms is too strong in 
many cases and does not give an accurate picture of uncertainty.
[...snip...]


Gergely, you are revisiting a line of thought that historically led to the 
introduction of more global treatments of atomic displacement.
These have distinct statistical and interpretational advantages.

Several approaches have been tried over the past 40 years or so.
The one that has proved most successful is the use of TLS
(Translation/Libration/Screw) models of bulk displacement to supplement or 
replace per-atom descriptions.  As you say, a per-atom treatment is often too 
strong and is not statistically justified by the experimental data.  I explored 
this with specific examples in

   "To B or not to B?" [Acta Cryst. 2012, D68, 468-477]
http://skuld.bmsc.washington.edu/~tlsmd/references.html

An NMR-style approach that constructs and refines multiple discrete models has 
been been re-invented several times. These treatments are generally called 
"ensemble models".  IMHO they are statistically unjustified and strictly worse 
than treatments based on higher level descriptions such as TLS or normal-mode 
analysis.
X-ray data is qualitatively different from NMR data, and optimal treatment of 
uncertainty must take this into account.

best regards

Ethan


> Hi,
> 
> It is enough to have Ų as unit to express uncertainty in 3D, but one can 
> express it with a single number only in a very specific case when the atom is 
> isotropic. Few atoms have a naturally isotropic distribution around their 
> mean position in very high resolution protein crystal structures. The 
> anisotropic atoms can be described by a 3x3 matrix, where each row and column 
> is associated with the uncertainty in a specific spatial direction. The 
> matrix elements are the product of the uncertainty in these directions. The 
> diagonal elements will be the square of uncertainty in the same direction and 
> they should be always positive, the off-diagonal combination of directions 
> are covariances (+,0 or -). In the end, every element will have a unit 
> distance*distance and the matrix will be symmetric. We cannot just take the 
> square root of the matrix elements and expect something meaningful, if for no 
> other reason the problem with negative covariances. To calculate the square 
> root on the matrix itself one has to diagonalize it first. The height of a 
> person in your example  sounds easy to define, but the mathematical formalism 
> will not decide that for me. I can also define height as the longest cord of 
> a person or the maximum elevation of a car mechanic under a car.  Through 
> diagonalization one can at least extract some interesting, intuitive, 
> principal directions. The final product, the sqrt(matrix), is not more 
> intuitive to me. To convert it to something intuitive I would have to 
> diagonalize square rooted matrix again. So shall we make an exception for the 
> special, isotropic description? Or 

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[Sotirios Sotiriou]

Dear All,



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- - -

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Head of Biology & Co-Founder

WSJ350.3.05, Lichtstrasse 35

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Tel: +41 (0) 788733686

  
sotirios.sotir...@forxtherapeutics.com

















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