You are lost without a map: Navigating the sea of protein structures
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Issue Date
2015-04Author
Lamb, Audrey L.
Kappock, Joseph
Silvaggi, Nicholas R.
Publisher
Elsevier
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
Metadata
Show full item recordAbstract
X-ray crystal structures propel biochemistry research like no other experimental method, since they answer many questions directly and inspire new hypotheses. Unfortunately, many users of crystallographic models mistake them for actual experimental data. Crystallographic models are interpretations, several steps removed from the experimental measurements, making it difficult for nonspecialists to assess the quality of the underlying data. Crystallographers mainly rely on “global” measures of data and model quality to build models. Robust validation procedures based on global measures now largely ensure that structures in the Protein Data Bank (PDB) are largely correct. However, global measures do not allow users of crystallographic models to judge the reliability of “local” features in a region of interest. Refinement of a model to fit into an electron density map requires interpretation of the data to produce a single “best” overall model. This process requires inclusion of most probable conformations in areas of poor density. Users who misunderstand this can be misled, especially in regions of the structure that are mobile, including active sites, surface residues, and especially ligands. This article aims to equip users of macromolecular models with tools to critically assess local model quality. Structure users should always check the agreement of the electron density map and the derived model in all areas of interest, even if the global statistics are good. We provide illustrated examples of interpreted electron density as a guide for those unaccustomed to viewing electron density.
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Citation
Audrey L. Lamb, T. Joseph Kappock, Nicholas R. Silvaggi
Biochim Biophys Acta. Author manuscript; available in PMC 2016 Oct 5.
Published in final edited form as: Biochim Biophys Acta. 2015 Apr; 1854(4): 258–268. Published online 2014 Dec 29. doi: 10.1016/j.bbapap.2014.12.021
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