Hi Catherine

Just a couple of ideas from my side:

- draw all the molecules (by symmetry) with a fairly large radius, to see the 
whole packing (you likely did, but in the pictures you shared, there’s only the 
ASU content). Maybe there’s little more to model actually

- your first picture does suggest some more can be modeled in: I would say 
always play around with the Fourier maps’ contours (both for the 2Fo-Fc/blue, 
as well for the diff Fo-Fc/green), especially lowering them. Noise will show up 
higher everywhere, but you might be able to discern more continuity in the 
spots you’re focusing on. Sometimes blurring (blurring/sharpening functions in 
coot) the map is also helpful for this, for a first interpreting task will 
reduce details, yet enhance low-resolution/envelope features. 

(nice to learn about modelcraft from ccp4, thanks Dave!)

my 2 cents
Ale


> On 6 Feb 2026, at 9:46 AM, David Briggs 
> <[email protected]> wrote:
> 
> Hi Catherine,
> 
> Have you shown the data to xtriage? (run by some pipelines at Diamond, or 
> available as a standalone program in Phenix). The output might give you some 
> hints. 
> 
> You don't say what your current r free is at the moment, but if your phases 
> are decent enough, I'd set modelcraft off on the data and go and get some 
> lunch. That software is imo akin to witchcraft and has saved me a lot of 
> manual tinkering to deliver a mostly complete asymmetric unit. It's found 
> extra copies I didn't know I had, and even revealed proteolytic fragments 
> that had been crystallised (I don't know how modelcraft behaved with coiled 
> coils, bit probably still worth a punt).
> 
> I'd also run Zanuda to check the space group (I always do this now, having 
> been tricked by crystals in the past).
> 
> Best of luck!
> 
> Dave
> 
> --
> Dr David C. Briggs CSci MRSB (he/him)
> Principal Laboratory Research Scientist, and
> Co-chair, Crick Staff Consultative forum
> Signalling and Structural Biology Lab
> The Francis Crick Institute
> London, UK
> Working hours Mon-Fri 0900-1700
> ==
> about.me/david_briggs <https://about.me/david_briggs> | OrcID 
> <https://orcid.org/0000-0002-9793-7339> | Google Scholar 
> <https://scholar.google.co.uk/citations?user=DRKG5wAAAAJ>
> ==
> "Would it not be better if one could really 'see' whether molecules...were 
> just as experiments suggested?"
> – Dorothy Hodgkin
> From: CCP4 bulletin board <[email protected] 
> <mailto:[email protected]>> on behalf of Catherine Back 
> <[email protected] 
> <mailto:[email protected]>>
> Sent: Friday, February 6, 2026 11:48:48 AM
> To: [email protected] <mailto:[email protected]> 
> <[email protected] <mailto:[email protected]>>
> Subject: [ccp4bb] Crystal pathology diagnosis please
>  
>  
> External Sender: Use caution.
>  
> 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] <mailto:[email protected]>
> 
> 
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