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  January 2008

CCP4BB January 2008

Options

Subscribe or Unsubscribe

Subscribe or Unsubscribe

Log In

Log In

Get Password

Get Password

Subject:

Re: bond lengths, angles, ideality and refinements

From:

Ian Tickle <[log in to unmask]>

Reply-To:

Ian Tickle <[log in to unmask]>

Date:

Wed, 9 Jan 2008 19:15:46 -0000

Content-Type:

text/plain

Parts/Attachments:

Parts/Attachments

text/plain (137 lines)

Hi William & others,

Indeed, phenix.refine uses cross-validation to optimise the scaling of the X-ray & B-factor weights.  All I did was demonstrate that you can do essentially the same thing as phenix.refine but using Refmac instead.  I don't claim to have done anything new, except I modified Refmac to print out the free likelihood and used that as a target function instead of Rfree, as suggested by Gerard Bricogne in Meth. Enzymol. (1997) 276, 361-423.  Whatever value of the RMSD (or better the RMS Z-score) comes out of that, you can be sure that it's based purely objectively on the experimental data, not on completely arbitrary and unjustifiable subjective choices, which is what Jaskolski et al. appear to be suggesting.  Cross-validation is a well-established methodology in statistics, it's certainly not 'numerology'!

Of course then you have to come up with some theory to explain the experimental results, i.e. why the RMSD that comes out must always be <= the RMS standard uncertainty, but actually that's not difficult since the RMSD is related to the accuracy and the SU is related to the precision, and on the face of it there's no reason why these should be related at all (as Gerard nicely demonstrated with his dartboard analogy in Leeds!).  Jaskolski et al.'s theory that always RMSD = <SU> regardless of resolution just doesn't fit the experimental results, and as every good scientist knows, it only takes one ugly fact to destroy a beautiful theory.

As you point out, setting a target value of 0.02 Ang or higher for the RMSD bonds and similarly for the angles, unless you have very high resolution data, will inevitably result in take-up of some fraction of the random experimental errors into the refined parameters, in order to inflate the RMSD/RMSZ's to their target values and reduce Rwork at the expense of Rfree - otherwise known as overfitting!  It's not recommended practice to deliberately cause random errors (however small) to be added to your co-ordinates!  This is obvious if you think about what happens at low resolution: there's no justification for refining individual xyz & B's, so the optimal procedure is to use constrained refinement with the torsion angles as parameters, or restrained refinement with *very* tight restraints (if that's feasible).  Whether you use constrained refinement or its restrained equivalent, it will keep the bond lengths & angles fixed at the initial dictionary values so the RMSD's will be identically zero, or very nearly so, throughout the refinement.

Someone mentioned 'experienced crystallographers': actually since the distinction between RMSD & SU is purely a question of statistics not of crystallography, any crystallographic experience is unlikely to be relevant!

The other question you raised is why Refmac doesn't refine the RMSD's much nearer to zero - this is something I also commented on; also why the Rfree & LLfree plots are so noisy compared with those from CNS & phenix.refine.  I think it's to do with rounding errors in the gradient calculation and/or optimisation code.  Refmac may be using single precision, whereas phenix.refine may be using double - I'm just guessing, maybe the programmers could comment?  This is something I would like to see improved, in order to make cross-validation with Refmac more reliable & useful.

Cheers

-- Ian

> -----Original Message-----
> From: [log in to unmask] 
> [mailto:[log in to unmask]] On Behalf Of William Scott
> Sent: 09 January 2008 17:32
> To: William Scott
> Cc: [log in to unmask]
> Subject: Re: [ccp4bb] bond lengths, angles, ideality and refinements
> 
> Sorry, that should have read
> 
> "because the value is established by social consensus, it is thus NOT
> guaranteed to be perfectly accurate, ..."
> 
> In other words, one can imagine some source of systematic error in
> establishing an ideal bond length.  For example, the crystal packing
> environment of small molecules might tend to distort a bond 
> by a couple
> hundredths of an Ångstrom.
> 
> 
> William Scott wrote:
> > Dear Yang Li:
> >
> >
> > Happy New Year to you, too, (ahead of Feb. 7th).
> >
> > You certainly owe us no apology; the reverse may not be true.
> >
> > Your question is an important one, as is what you have 
> written below.
> >
> > I'm not certain I have a completely satisfactory answer.
> >
> > The reason is that ideal bond lengths may or may not be 
> "true" in the
> > sense that the value is established by social consensus, and is thus
> > guaranteed to be perfectly accurate, even though it may be 
> quite precise.
> >
> > Because of this, and because of natural deviations from 
> ideality (which
> > really only become trustworthy observations at extremely 
> high resolution),
> > a certain amount of "wiggle room" is typically allowed in 
> terms of rmsd.
> >
> > The more conservative the refinement, the smaller the rmsd 
> from ideality
> > will be.
> >
> > Some people believe 0.02 Å deviation from ideality is 
> reasonable, based on
> > the accuracy of the dictionary values of bond lengths and 
> angles; others
> > consider that to be "too sloppy" and a way to artificially deflate
> > Rfactors.
> >
> > I seem to have detected a tendency in the literature to aim 
> for about 0.01
> > Å deviation.  The new refinement program phenix.refine, 
> which is supposed
> > to optimize weighting between X-ray terms and 
> stereochemical constraints
> > automatically, seems to settle in at quite conservative 
> values, such as
> > 0.005 Å, whereas with refmac, I can't seem to get the 
> geometry any more
> > ideal than 0.005 Å even if I try to idealize a structure in 
> the absence of
> > X-ray data.
> >
> > So, like you, I am a bit confused, and wouldn't mind 
> hearing more from the
> > experts.
> >
> > All the best,
> >
> > Bill
> >
> >
> >
> >
> >
> >
> > yang li wrote:
> >> Dear All,
> >>       I am very sorry to involve you into such insignificance
> >> discussion,
> >> I
> >> have reached agreement
> >> with Prof Gerard, please stop talking about things beyond science,
> >> thanks!
> >>       I read a book today, which said "A refined model 
> should exhibit
> >> rms
> >> deviations of no more
> >> than 0.02A for bond length and 4 for bond angels", I just 
> wonder about
> >> the
> >> standard of the
> >> bond length and the bond angel. I think most of you have 
> read similar
> >> words!
> >> But maybe I
> >> didnot express clearly and made some phrasal mistakes.
> >>       At last, happy new year to you all--though very late!
> >>
> >>
> >> Sincerely!
> >> Yang Li
> >>
> >
> 
> 


Disclaimer
This communication is confidential and may contain privileged information intended solely for the named addressee(s). It may not be used or disclosed except for the purpose for which it has been sent. If you are not the intended recipient you must not review, use, disclose, copy, distribute or take any action in reliance upon it. If you have received this communication in error, please notify Astex Therapeutics Ltd by emailing [log in to unmask] and destroy all copies of the message and any attached documents. 
Astex Therapeutics Ltd monitors, controls and protects all its messaging traffic in compliance with its corporate email policy. The Company accepts no liability or responsibility for any onward transmission or use of emails and attachments having left the Astex Therapeutics domain.  Unless expressly stated, opinions in this message are those of the individual sender and not of Astex Therapeutics Ltd. The recipient should check this email and any attachments for the presence of computer viruses. Astex Therapeutics Ltd accepts no liability for damage caused by any virus transmitted by this email. E-mail is susceptible to data corruption, interception, unauthorized amendment, and tampering, Astex Therapeutics Ltd only send and receive e-mails on the basis that the Company is not liable for any such alteration or any consequences thereof.
Astex Therapeutics Ltd., Registered in England at 436 Cambridge Science Park, Cambridge CB4 0QA under number 3751674

Top of Message | Previous Page | Permalink

JiscMail Tools


RSS Feeds and Sharing


Advanced Options


Archives

March 2024
February 2024
January 2024
December 2023
November 2023
October 2023
September 2023
August 2023
July 2023
June 2023
May 2023
April 2023
March 2023
February 2023
January 2023
December 2022
November 2022
October 2022
September 2022
August 2022
July 2022
June 2022
May 2022
April 2022
March 2022
February 2022
January 2022
December 2021
November 2021
October 2021
September 2021
August 2021
July 2021
June 2021
May 2021
April 2021
March 2021
February 2021
January 2021
December 2020
November 2020
October 2020
September 2020
August 2020
July 2020
June 2020
May 2020
April 2020
March 2020
February 2020
January 2020
December 2019
November 2019
October 2019
September 2019
August 2019
July 2019
June 2019
May 2019
April 2019
March 2019
February 2019
January 2019
December 2018
November 2018
October 2018
September 2018
August 2018
July 2018
June 2018
May 2018
April 2018
March 2018
February 2018
January 2018
December 2017
November 2017
October 2017
September 2017
August 2017
July 2017
June 2017
May 2017
April 2017
March 2017
February 2017
January 2017
December 2016
November 2016
October 2016
September 2016
August 2016
July 2016
June 2016
May 2016
April 2016
March 2016
February 2016
January 2016
December 2015
November 2015
October 2015
September 2015
August 2015
July 2015
June 2015
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


JiscMail is a Jisc service.

View our service policies at https://www.jiscmail.ac.uk/policyandsecurity/ and Jisc's privacy policy at https://www.jisc.ac.uk/website/privacy-notice

For help and support help@jisc.ac.uk

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