Whaddaya Know: A Guide to Uncertainty and Subjectivity in Structural Biology

The methods of structural biology, while powerful, are technically complex. Although the Protein Data Bank (PDB) provides a repository that allows anyone to download any structure, many users would not appreciate the caveats that should be considered when examining a structure. Here, we describe several key uncertainties associated with the application of X-ray crystallography, NMR spectroscopy, single-particle electron microscopy (SPEM), and small-angle scattering (SAS) to biological macromolecules. The take-home message is that structures are not absolute truths – they are models that fit the experimental data and therefore have uncertainty and subjectivity associated with them. These uncertainties must be appreciated – careful reading of the associated paper, and any validation report provided by the structure database, is highly recommended.