Obviously, we can mathematically separate the position of an atom from its type. Note that a prerequisite for this subtraction of patterns is that they remain isomorphous, i.e., we do not change the structural terms in the structure factor summation. We still cannot use a Fourier synthesis to fins the electron density of the heavy atoms, because we still lack their phases. This map contains peaks at the distance vectors between atoms in the structure. P gets large very rapidly, and for ease of interpretation we want only few atoms in the derivative.
Some sophisticated methods can actually solve quite large numbers of atoms, up into the hundreds.
This is mostly important for MAD phasing . Once heavy atom positions of two derivatives are determined, MIR phasing equations can be solved and initial protein phases determined. Another source of electronic differences The electronic differences needed to create difference maps from which the heavy atom positions and initial protein phases can be solved, can originate from ANY kind of differences in scattering behavior. This is usually done at a synchrotron , where narrow bandwidth monochromators are used to vary the wavelength of the synchrotron radiation emanating from an electron beam circling in a storage ring. The method also creates difference maps between and within data sets recorded at different wavelengths which are solved and usually quite excellent protein phases are obtained.