When you say you have poor anomalous signal, do you mean the CCanom (and other 
anomalous stats) are poor even in the lower resolution shells?
Perhaps some more experienced people could advise on potentially merging 
multiple crystal datasets to boost the signal via redundancy.

Also the anomalous atoms are affected by radiation damage faster than the 
structure overall, so optimising processing to remove radiation damaged batches 
might help get you over the line?

The sel-met approach has its advantages but my experience is that it requires a 
more carefully planned experiment vs super heavy SAD approaches like TEW (which 
I am a huge advocate for).
This is off topic, but you can even solve your structures sometimes by doing MR 
with TEW alone!

The only advice I would venture is that cracking a difficult case with sub 
optimal data may rely on being able to discriminate between a real solution 
that is poor quality and a nonsense solution that is also poor quality.

My first approach is to run Crank2 (shelx, phaser, parrot) or phenix autosol 
and terminate at solvent flattening with PARROT and then inspect the maps.

Look for a delineation between solvent channels and protein-like features,  
does it form a proper lattice? Perhaps blur the map to see if it becomes 
clearer.

Basically, if you know you have very little anomalous signal then you can't 
assume it will be possible to get an accurate substructure and good initial 
phases,  but if you are able to get something that is undeniably real (i.e a 
distorted noisy version of the "true" map) then you should gradually be able to 
bootstrap up to a model that can take over.

There have been some structures where I had sel-met data and later solved the 
structure by another method only to realise that the sel MET SAD map was 
correct, just horribly noisy.

Best wishes

Matthew.

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Sent: Saturday, July 11, 2026 12:41 pm
To: [email protected] <[email protected]>
Subject: [ccp4bb] SAD

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Dear all,
I am currently processing a SAD dataset collected from a Se-Met derivative. 
According to the matthews_coef calculation in CCP4, there should be 20 heavy 
atom sites in the asymmetric unit.
However, due to the very weak anomalous signal, the occupancy refinement in 
SHELX shows only one site with an occupancy above 1.0, one site around 0.4, and 
the remaining 15 sites all converging to approximately 0.3.
Given this situation, I would be very grateful for any suggestions on how to 
obtain reliable initial phases. Are there any specific strategies, software 
settings, or alternative approaches (e.g., density modification or partial 
structure refinement) that you would recommend to make the most of this weak 
signal?
Thank you in advance for your time and insights.
Best regards,
Kai Zhang


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