Other limitations of crystallographic models

The limitations discussed so far apply to all models and suggest questions that the user of crystallographic results should ask routinely. Other limitations are special cases that may or may not apply to a given model. It is important to read the original publications of a structure to see whether any of the following limitations apply. 

Not all published models are refined to high resolution. For instance, publication of a low-resolution structure may be warranted if it displays an interesting and suggestive arrangement of cofactors or clusters of metal ions, provides possible insights into conformations of a new family or proteins, or displays the application of new imaging methods. In some cases, the published structure is only a 

Occasionally, portions of the known sequence of a protein are never found in the electron-density maps, presumably because the region is highly disordered or in motion, and thus invisible on the time scale of crystallography. It is not at all uncommon for residues at termini, especially the N terminus, to be missing from a model. Discussions of these structure-specific problems are included in a thorough refinement paper, as well as in PDB header information. 

Just as the auto mechanic sometimes has parts left over, electron-density maps occasionally show clear, empty density after all known contents of the crystal have been located. Apparent density can appear as an artifact of missing Fourier terms, but this density disappears when a more complete set of data is obtained. Among the possible explanations for density that is not artifactual are ions like phosphate and sulfate from the mother liquor reagents like mercaptoethanol, dithiothreitol, or detergents used in purification or crystallization or cofactors, inhibitors, allosteric effectors, or other small molecules that survived the protein purification. Later discovery of previously unknown but important ligands has sometimes resulted in subsequent interpretation of empty density. 

Refinement papers should also mention any evidence that the protein is affected by crystallization. Packing effects may be evident in the model itself. For example, packing may induce slight differences between what are otherwise 

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