JiscMail Logo
Email discussion lists for the UK Education and Research communities

Help for CCP4BB Archives


CCP4BB Archives

CCP4BB Archives


CCP4BB@JISCMAIL.AC.UK


View:

Message:

[

First

|

Previous

|

Next

|

Last

]

By Topic:

[

First

|

Previous

|

Next

|

Last

]

By Author:

[

First

|

Previous

|

Next

|

Last

]

Font:

Proportional Font

LISTSERV Archives

LISTSERV Archives

CCP4BB Home

CCP4BB Home

CCP4BB  March 2011

CCP4BB March 2011

Options

Subscribe or Unsubscribe

Subscribe or Unsubscribe

Log In

Log In

Get Password

Get Password

Subject:

Re: The meaning of B-factor, was Re: [ccp4bb] what to do with disordered side chains

From:

Zbyszek Otwinowski <[log in to unmask]>

Reply-To:

[log in to unmask]

Date:

Thu, 31 Mar 2011 17:14:44 -0500

Content-Type:

text/plain

Parts/Attachments:

Parts/Attachments

text/plain (156 lines)

Dale Tronrud wrote:
>    While what you say here is quite true and is useful for us to
> remember, your list is quite short.  I can add another
> 
> 3) The systematic error introduced by assuming full occupancy for all 
> sites.

You are right that structural heterogeneity is an additional factor.
Se-Met expression is one of the examples where the Se-Met residue is 
often not fully incorporated, and therefore its side chains have mixed 
with Met composition.
Obviously, solvent molecules may have partial occupancies.
Also, in heavily exposed crystals chemical reactions result in loss of 
the functional groups (e.g. by decarboxylation).
However, in most cases even if side chains have multiple conformations 
their total occupancy is 1.0.

> 
> There are, of course, many other factors that we don't account for
> that our refinement programs tend to dump into the B factors.
> 
>    The definition of that number in the PDB file, as listed in the mmCIF
> dictionary, only includes your first factor --
> 
> http://mmcif.rcsb.org/dictionaries/mmcif_std.dic/Items/_atom_site.B_iso_or_equiv.html 
> 
> 
> and these numbers are routinely interpreted as though that definition is
> the law.  Certainly the whole basis of TLS refinement is that the B factors
> are really Atomic Displacement Parameters.   In addition the stereochemical
> restraints on B factors are derived from the assumption that these 
> parameters
> are ADPs.  Convoluting all these other factors with the ADPs causes serious
> problems for those who analyze B factors as measures of motion.
> 
>    The fact that current refinement programs mix all these factors with the
> ADP for an atom to produce a vaguely defined "B factor" should be 
> considered
> a flaw to be corrected and not an opportunity to pile even more factors 
> into
> this field in the PDB file.
> 

B-factors describe overall uncertainty of the current model. Refinement 
programs, which do not introduce or remove parts of the model (e.g. are 
not able to add additional conformations) intrinsically pile up all 
uncertainties into B-factors. Solutions, which you would like to see 
implemented, require a model-building like approach. The test of the 
success of such approach would be a substantial decrease of R-free 
values. If anybody can show it, it would be great.

Zbyszek

> Dale Tronrud



> 
> On 3/31/2011 9:06 AM, Zbyszek Otwinowski wrote:
>> The B-factor in crystallography represents the convolution (sum) of two
>> types of uncertainties about the atom (electron cloud) position:
>>
>> 1) dispersion of atom positions in crystal lattice
>> 2) uncertainty of the experimenter's knowledge  about the atom position.
>>
>> In general, uncertainty needs not to be described by Gaussian function.
>> However, communicating uncertainty using the second moment of its
>> distribution is a widely accepted practice, with frequently implied
>> meaning that it corresponds to a Gaussian probability function. B-factor
>> is simply a scaled (by 8 times pi squared) second moment of uncertainty
>> distribution.
>>
>> In the previous, long thread, confusion was generated by the additional
>> assumption that B-factor also corresponds to a Gaussian probability
>> distribution and not just to a second moment of any probability
>> distribution. Crystallographic literature often implies the Gaussian
>> shape, so there is some justification for such an interpretation, where
>> the more complex probability distribution is represented by the sum of
>> displaced Gaussians, where the area under each Gaussian component
>> corresponds to the occupancy of an alternative conformation.
>>
>> For data with a typical resolution for macromolecular crystallography,
>> such multi-Gaussian description of the atom position's uncertainty is not
>> practical, as it would lead to instability in the refinement and/or
>> overfitting. Due to this, a simplified description of the atom's position
>> uncertainty by just the second moment of probability distribution is the
>> right approach. For this reason, the PDB format is highly suitable for 
>> the
>> description of positional uncertainties,  the only difference with other
>> fields being the unusual form of squaring and then scaling up the 
>> standard
>> uncertainty. As this calculation can be easily inverted, there is no loss
>> of information. However, in teaching one should probably stress more this
>> unusual form of presenting the standard deviation.
>>
>> A separate issue is the use of restraints on B-factor values, a subject
>> that probably needs a longer discussion.
>>
>> With respect to the previous thread, representing poorly-ordered (so
>> called 'disordered') side chains by the most likely conformer with
>> appropriately high B-factors is fully justifiable, and currently is
>> probably the best solution to a difficult problem.
>>
>> Zbyszek Otwinowski
>>
>>
>>
>>>>> - they all know what B is and how to look for regions of high B
>>>>> (with, say, pymol) and they know not to make firm conclusions about
>>>>> H-bonds
>>>>> to flaming red side chains.
>>>>
>>>> But this "knowledge" may be quite wrong.  If the flaming red really
>>>> indicates
>>>> large vibrational motion then yes, one whould not bet on stable 
>>>> H-bonds.
>>>> But if the flaming red indicates that a well-ordered sidechain was
>>>> incorrectly
>>>> modeled at full occupancy when in fact it is only present at
>>>> half-occupancy
>>>> then no, the H-bond could be strong but only present in that
>>>> half-occupancy
>>>> conformation.  One presumes that the other half-occupancy location
>>>> (perhaps
>>>> missing from the model) would have its own H-bonding network.
>>>>
>>>
>>> I beg to differ.  If a side chain has 2 or more positions, one should 
>>> be a
>>> bit careful about making firm conclusions based on only one of those, 
>>> even
>>> if it isn't clear exactly why one should use caution.  Also, isn't the
>>> isotropic B we fit at "medium" resolution more of a "spherical cow"
>>> approximation to physical reality anyway?
>>>
>>>    Phoebe
>>>
>>>
>>>
>>
>>
>> Zbyszek Otwinowski
>> UT Southwestern Medical Center at Dallas
>> 5323 Harry Hines Blvd.
>> Dallas, TX 75390-8816
>> Tel. 214-645-6385
>> Fax. 214-645-6353
> 


-- 
Zbyszek Otwinowski
UT Southwestern Medical Center	
5323 Harry Hines Blvd., Dallas, TX 75390-8816
(214) 645 6385 (phone) (214) 645 6353 (fax)
[log in to unmask]

Top of Message | Previous Page | Permalink

JiscMail Tools


RSS Feeds and Sharing


Advanced Options


Archives

May 2015
April 2015
March 2015
February 2015
January 2015
December 2014
November 2014
October 2014
September 2014
August 2014
July 2014
June 2014
May 2014
April 2014
March 2014
February 2014
January 2014
December 2013
November 2013
October 2013
September 2013
August 2013
July 2013
June 2013
May 2013
April 2013
March 2013
February 2013
January 2013
December 2012
November 2012
October 2012
September 2012
August 2012
July 2012
June 2012
May 2012
April 2012
March 2012
February 2012
January 2012
December 2011
November 2011
October 2011
September 2011
August 2011
July 2011
June 2011
May 2011
April 2011
March 2011
February 2011
January 2011
December 2010
November 2010
October 2010
September 2010
August 2010
July 2010
June 2010
May 2010
April 2010
March 2010
February 2010
January 2010
December 2009
November 2009
October 2009
September 2009
August 2009
July 2009
June 2009
May 2009
April 2009
March 2009
February 2009
January 2009
December 2008
November 2008
October 2008
September 2008
August 2008
July 2008
June 2008
May 2008
April 2008
March 2008
February 2008
January 2008
December 2007
November 2007
October 2007
September 2007
August 2007
July 2007
June 2007
May 2007
April 2007
March 2007
February 2007
January 2007


WWW.JISCMAIL.AC.UK

Secured by F-Secure Anti-Virus CataList Email List Search Powered by the LISTSERV Email List Manager