[phenixbb] XN-refinement

Tim Gruene tim.gruene at psi.ch
Fri Oct 14 07:51:18 PDT 2016

Hi Pavel,

in 1978, there was a version of shelxl for joint refinement of X-ray and 
neutron data (Orpen, Pippard, Sheldrick, Acta Cryst (1978) B34 2466-2472)
The paper now cited for the Hirshfeld test (Acta Cryst A32 (1976) pp239) 
discusses the combination of refinement against neutron and X-ray data, 
including many references to Phil Coppens, although I cannot tell if this 
refers to joint refinement.

I appreciate your summary, it matches the conclusions about refinement against 
neutron data I mentioned earlier, to use the X-ray data as information for 

For macromolecular data, the restraints often contribute greatly to the data 
to parameter ratio, e.g. for a shelxl refinement of 1L2K, there are about 1300 
reflections, 40,000 restraints and 9,000 parameters. And since the starting 
structure has often already been refined against the X-ray data anyhow, why do 
it again and risk a mix-up with your points of interest?


On Friday, October 14, 2016 10:09:55 PM Pavel Afonine wrote:
> Hi Johannes,
> historically, in joint Xray+Neutron refinement first tried by Coppens et
> al (1981) in small molecule world and later (1982) by Wlodawer &
> Hen­drickson in bio-macromolecules, and way later implemented in
> refinement tools such as nCNS (2009) and Phenix (2010), one single model
> is refined against two data sets, Xray and neutron.
> The rationale to use two data sets, Xray and neutron, is to alleviate
> the seemingly poor data-to-parameters ratio because H and D are used
> explicitly in refinement using neutron data. This is all discussed in
> great details in that 6 years old paper:
> https://www.phenix-online.org/papers/dz5209_reprint.pdf
> Turns out with a proper data / restraints weight the problem of
> data-to-parameters amount is not as bad as it may appear, since by
> varying the weight one can dose the amount of a priori knowledge
> (restraints) as desired. This makes it possible to refine one model
> against X-ray or neutron data individually without problems.
> Also, we know that X-H distances for X-ray and neutron are different
> (X-ray are shorter a tiny bit). We also know that both data sets may be
> collected at different temperatures (neutron at room, and X-ray at
> cryo), which means B factors are going to be different, some rotamers
> may be different, water structure may be slightly different, and so on.
> All in all we really do need to have two structures to maximize the use
> of available information. This is the new refinement paradigm that's
> being implemented in phenix.refine and will become available at some point.
> The best you can do right now is:
> 1) Get the best possible refined X-ray structure (refined against x-ray
> data set alone);
> 2) Use refined x-ray structure as a starting point for neutron
> refinement (add H,D as appropriate - trivially done using
> phenix.ready_set or using Phenix GUI);
> 3) Refine structure from #2 against neutron data set alone. This will
> make sure H and D have identical coordinates and B. If really needed you
> can supply X-ray structure as a reference model - also trivially done
> from the phenix.refine GUI.
> Let us know should you have questions or need help.
> Pavel
> On 10/13/16 23:06, Johannes Schiebel wrote:
> > Hi everyone,
> > 
> > I am currently working on an X-ray/neutron (XN) joint refinement using
> > phenix.refine. As it should be, H/D coordinates and ADPs at
> > exchangable sites are refined to equal values when using Phenix
> > version 1.10.1-2155 and neutron data only. This is also stated in the
> > paper describing the development of the method (Afonine et al. (2010)
> > Joint X-ray and neutron refinement with phenix.refine. Acta
> > Crystallogr D Biol Crystallogr 66, 1153-1163) as the default behavior:
> > "Currently, phenix.refine maintains the H and D atoms at coinciding
> > positions and constrains their ADPs to be equal to each other".
> > However, when switching to XN-refinement using the same Phenix
> > version, H and D atoms refine to different coordinates and ADPs, which
> > should not be the case as it leads to unrealistic artifacts as can be
> > seen from the deposited PDB 3X2P:
> > 
> > ATOM    186  H  AALA A  13       3.486 -18.200 -14.123  0.38
> > 14.54           H
> > ATOM    187  D  BALA A  13       3.488 -18.195 -14.111  0.62
> > 38.07           D
> > 
> > In this example, the D-occupancy is likely overestimated, while the
> > H-occupancy is underestimated because the ADPs refine to very
> > different values, which is chemically not reasonable.
> > 
> > Hence my question: How can I treat my data in a way that ADPs and
> > coordinates refine to the same values at exchangeable H/D sites also
> > for XN-refinement? Is there a specific keyword I am currently
> > overlooking or do I have to use another Phenix version?
> > 
> > I would be really glad to receive your feedback. Thanks in advance!
> > 
> > Kind regards,
> > Johannes
> > 
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Paul Scherrer Institut
Dr. Tim Gruene
- persoenlich -
Principal Investigator
Biology and Chemistry
CH-5232 Villigen PSI

Phone: +41 (0)56 310 5297


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