High-quality three-dimensional structural data is of great value for the functional interpretation of biomacromolecules, especially proteins; however, structural quality varies greatly across the entries in the worldwide Protein Data Bank (wwPDB). Since 2008, the wwPDB has required the inclusion of structure factors with the deposition of x-ray crystallographic structures to support the independent evaluation of structures with respect to the underlying experimental data used to derive those structures. However, interpreting the discrepancies between the structural model and its underlying electron density data is difficult, since derived sigma-scaled electron density maps use arbitrary electron density units which are inconsistent between maps from different wwPDB entries. Therefore, we have developed a method that converts electron density values from sigma-scaled electron density maps into units of electrons. With this conversion, we have developed new methods that can evaluate specific regions of an x-ray crystallographic structure with respect to a physicochemical interpretation of its corresponding electron density map. We have systematically compared all deposited x-ray crystallographic protein models in the wwPDB with their underlying electron density maps, if available, and characterized the electron density in terms of expected numbers of electrons based on the structural model. The methods generated coherent evaluation metrics throughout all PDB entries with associated electron density data, which are consistent with visualization software that would normally be used for manual quality assessment. To our knowledge, this is the first attempt to derive units of electrons directly from electron density maps without the aid of the underlying structure factors. These new metrics are biochemically-informative and can be extremely useful for filtering out low-quality structural regions from inclusion into systematic analyses that span large numbers of PDB entries. Furthermore, these new metrics will improve the ability of non-crystallographers to evaluate regions of interest within PDB entries, since only the PDB structure and the associated electron density maps are needed. These new methods are available as a well-documented Python package on GitHub and the Python Package Index under a modified Clear BSD open source license.
Digital Object Identifier (DOI)
HNBM received National Science Foundation (https://www.nsf.gov/) award 1419282.
An older version of this manuscript is available on the bioRxiv preprint server: https://doi.org/10.1101/613109. Also the described software is available on GitHub (https://github.com/MoseleyBioinformaticsLab/pdb_eda) and the Python Package Index (https://pypi.org/project/pdb-eda/), the documentation is available on ReadTheDocs (https://pdb-eda.readthedocs.io/en/latest/), and all results are available on a FigShare repository (https://doi.org/10.6084/m9.figshare.7994294).
Yao, Sen and Moseley, Hunter N. B., "A Chemical Interpretation of Protein Electron Density Maps in the Worldwide Protein Data Bank" (2020). Molecular and Cellular Biochemistry Faculty Publications. 176.
S1 Table. Atom type mapping and the electron counts for the 20 common residues. https://doi.org/10.1371/journal.pone.0236894.s001
pone.0236894.s002.docx (13 kB)
S2 Table. Atom-specific electron counts for the 20 common residues. https://doi.org/10.1371/journal.pone.0236894.s002
pone.0236894.s003.tiff (599 kB)
S1 Fig. Density plot of the median chain deviation fraction for all structures in the PDB of different resolutions. https://doi.org/10.1371/journal.pone.0236894.s003