Thank you all for the prompt responses and suggestions.

My metal ion of interest is Cesium in this case, so I guess I am more interested in using this approach for visualization rather than peak identification - the strong density of Cs is fairly obvious

I have attached a few images of the superimposed (Fo, Phi) maps and resulting difference map using either Superpose maps in phenix or transform_map in coot following Tim's suggestions.

I also tried using maprot (CCP4) to apply the rotation/translation operator from the LSQ superpose but the resulting map was not superposed correctly (not sure why).

Both results seem kind of reasonable - I have shown one of the difference peaks for what is likely to be a bound Cs. For both approaches the peak was very obvious at a 3 sigma level, and could still be observed to around 10 sigma in both cases. I am still unsure about differences in scaling, so although strong positive peaks can be identified, I wouldn't be confident using the map to interpret smaller differences.

In response to Eric - I checked the anomalous signal, which was fairly weak. The resulting anomalous difference map did show positive peaks up to a level of ~10 sigma that matched those observed in the above real-space difference maps, with a 3 sigma level corresponding to 0.0137 e/A^3. The CCanom was also low (1-5% between shells), so I was thinking that another approach might be more suitable for this data?

Cheers,

Jordan