Hello Catherine,

I’m also an idiot so all my sympathy, and please don’t feel offended by my 
questions:

  *   Is it only autoprocessing, or have you also tried to place additional 
copies with let’s say Molrep, or Phaser?
  *   To me it looks like your map is less anisotropic than it should look if 
you only had those helices in, and the additional density looks like 2 more 
bundles orthogonal to your current solution. Those could be fragments of the 
same thing? I’d try placing PolySer helical fragments, say 50% the current 
length or even shorter, on the top of your current solution which looks good, 
actually – at least the contrast with solvent is good, so in principle I do not 
believe there is any pathology just based on the information you gave. You seem 
to have enough resolution to fit individual helices, not necessarily bundles. 
If you are lazy and lucky (better than 2.5 angstroms), try Arcimboldo. There is 
also Shelx…E, I think, that amplifies the density with density modification 
based on MR solution and … Phenix Autosolve (sorry to mention it here ;)
  *   Coiled-coils can get to really low solvent content (on the 40%, maybe 
less?), my guess is that your crystals could also be really dry, even though I 
am not familiar with those kinds of bundles. So if the autoprocessing is taking 
the normal solvent contents as a limit, it could be possibly underestimating 
the number of copies in the AU, I think. I am not familiar with DLS 
autoprocessing either.

OK well, I might be completely off, and it won’t be the first time, I’ll be 
looking forward to read what others have to say about this. Please keep us 
posted of whatever will have worked for you at the end.

Cheers

---------------------------------------------------
Carlos KIKUTI, PhD
Structural Motility Team
UMR144 - CNRS - Institut Curie
12 rue Lhomond - 75005 Paris, France
[email protected]<mailto:[email protected]>



De : CCP4 bulletin board <[email protected]> au nom de Catherine Back 
<[email protected]>
Répondre à : Catherine Back <[email protected]>
Date : vendredi 6 février 2026 à 12:50
À : "[email protected]" <[email protected]>
Objet : [ccp4bb] Crystal pathology diagnosis please

Morning All,

My colleague and I are trying to solve the structure of a long, alpha helical 
bundle protein. We thought it had solved well with 2 molecules in the AU (which 
had decent stats), but upon a closer look there are very large 'solvent 
channels' in the lattice, with green/blue density within. It looks like there 
are protein molecules, positioned lengthways to the molecules in the AU, within 
these channels which the autoprocessing (at Diamond Light Source) is not 
picking up. See images attached.

I now have the image files and have been reprocessing them using xia2-DIALS in 
ccp4i2.

I am unsure what kind of crystal pathology we're dealing with here. There is no 
twinning warnings or anything else really that the processing has identified. 
The space group is always identified as P212121, unit cell 34.8, 184.8, 202.3, 
90.0, 90.0, 90.0.

I've tried quite a few different things to get the software to fit molecules 
into the density, including manually extending the unit cell, but all the 
outputs have been wrong or had really bad stats. I'm wondering if the indexing 
is wrong, but I'm not sure how to sort this. There is clearly something going 
on here, which is either really obvious (that I'm not identifying because I'm 
an idiot) or it's something more complex.

Any ideas/help will be much appreciated.

Best wishes,
Catherine Back


Dr Catherine R. Back (she/her)

Senior Post-doctoral Research Associate

School of Biochemistry
University of Bristol

UK



[email protected]



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