I am not an xray crystallographer, but from what I've heard there's often a good deal of guess work and intuition involved in the process of fitting a ball-and-stick molecular model to a crystal-derived electron density map. This guess work tends to introduce a substantial amount of error into the the final set of atomic coordinates.
The quantum mechanical simulation programs that I have tried (Gaussian, Gamess) use atomic coordinates as their input. Are there any QM methods that directly utilize the information contained in an electron density map, either in conjunction with or instead of atomic coordinates?
If there isn't currently a QM software package that can directly incorporate electron density data, would it be theoretically possible to make one? It seems like it would be a good way to eliminate some of the errors introduced durring atomic fitting, and to move the source of the simulation's input one step closer to the actual experimental data. Could electron density data be useful for simulations, or am I just being delusional?
If there are any structural biologists and/or QM macromolecule simulators in the house, please help me sort this out.