ZBH
ZBHCenter for Bioinformatics
Molecular Modelers Should Know Their Electron Density
9 October 2017
X-ray crystallography is the backbone of modern, structure-based molecular drug design. While protein structures are easily accessible via the PDB and frequently used, it is to our experience not common practice to inspect the original experimental data, the electron density. Typically, only global measures like resolution or R_free are taken into account when structures are selected for modeling endevors. Since the electron density support can substantially vary within a structure, a deeper look into the experimental data is highly recommended. Also, method developers should have a second look before deriving statistical models or computer algorithms from protein structures.
RSCC and RSR as the methods widely in use are based on a comparison of electron density with a density map reconstructed from the structure model. Besides being underspecified, they do not take superfluous density and overlapping electron density spheres from noncovalently bound atoms into account. Furthermore, the resulting values depend on the map reconstruction step which might get time consuming.
To lower the barrier for non-crystallographers to compare structure models with electron density, we developed EDIA, a fairly straightforward calculation scheme creating density support values for each individual atom. The resulting numbers can be easily visualized or used to automatically filter large structure collections. To get an impression, have a look at your preferred PDB structure within our ProteinsPlus webserver. EDIA is also available for local use as part of our NAOMI ChemBio Suite. The EDIA approach is described in detail in a recent article appeared in Journal of Chemical Information and Modeling: http://pubs.acs.org/doi/10.1021/acs.jcim.7b00391
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