14 Oct
2016
14 Oct
'16
11:51 a.m.
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 restraints. 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? Cheers, Tim 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 > > > > _______________________________________________ > > phenixbb mailing list > > [email protected] > > http://phenix-online.org/mailman/listinfo/phenixbb > > Unsubscribe: [email protected] > > _______________________________________________ > phenixbb mailing list > [email protected] > http://phenix-online.org/mailman/listinfo/phenixbb > Unsubscribe: [email protected] -- -- Paul Scherrer Institut Dr. Tim Gruene - persoenlich - Principal Investigator Biology and Chemistry OFLC/102 CH-5232 Villigen PSI Phone: +41 (0)56 310 5297 GPG Key ID = A46BEE1A