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.


2 Answers 2


I do not think this would be useful and am not aware of it being implemented anywhere, but as they say, absence of evidence is not evidence of absence. I saw a lecture a while back about research by Reimers and coworkers concerning the use of ab initio methods in the final refinement of XRD fits, in addition to the restrained MD often used in refinement, however this is quite distinct from using the ESD map to prime a calculation.

In XRD, the electron density map is a proxy for the nuclear coordinates, whereas in QM calculations, the electron density is a function of the nuclear coordinates and can be obtained fairly easily* by convergence from a guess wavefunction. Using the electron density as the sole input for a QM calculation would still require an initial guess at the nuclear coordinates, as without those you do not have a nuclear potential with which to make the QM calculation meaningful.

QM calculations can of course be extremely useful in attempting to elucidate contentious XRD structures, where several interpretations of a structure or structures may exist. The ability to garner extra electronic structure information from a QM calculation means that you can also attempt to reconcile your QM model with other experimental techniques like EPR, NMR, etc. This allows researchers to connect suites of data that would otherwise be independent.

I hope this is interesting to you!



You could perhaps try Hydromic, or iMODFIT


Solution properties of macromolecules and macromolecular complexes with a 3D density map, obtained by cryo-electron microscopy or other techniques


iMODFIT is an efficient tool for flexible fitting of atomic structures into EM maps based on Normal Mode Analysis in internal Coordinates.


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