Techniques, tools and best practices for ligand electron-density analysis and results from their application to deposited crystal structures

Acta Cryst. (2013). D69, 150-167 (http://doi.org/ksj)

Missing density: extended glycosylations. The specific conformation of the last three α-D-mannose moieties (A5-A7) of the extended branched glycosylation in PDB entry 3ib0 [Mir et al. (2009). Biophys. J. 97, 3178-3186] is unsupported by electron density in the structure of bovine lactotransferrin, while the first two sugar moieties (A3-A4) are clearly present. The 1.4 Å resolution mF_o − DF_c map contoured at +3σ (green) was calculated after refining a model omitting the sugar moieties of the glycosylation site.

Determining protein structures in complex with a small-molecule ligand is essential to the understanding of biologically important molecular interactions and in drug design. Electron density is the primary evidence which supports a particular ligand-binding mode in a corresponding complex structure. Inspection of deposited structure models reveals low real-space correlation coefficients for a large number of small-molecule ligands. Several classes of detected problems are analyzed, and suggestions for improvement in training of crystallographers and model validation are provided.