On the validation of crystallographic symmetry and the quality of structures

In 2008, Zwart and colleagues observed that the fraction of the structures deposited in the PDB alleged to have pseudosymmetry or special noncrystallographic symmetry (NCS) was about 6%, and that this percentage was rising annually. A few years later, Poon and colleagues found that 2% of all the crystal structures in the PDB belonged to higher symmetry space groups than those assigned to them. Here, I report an analysis of the X-ray diffraction data deposited for this class of structures, which shows that most of the pseudosymmetry and special NCS that has been reported is in fact true crystallographic symmetry (CS). This distinction is important because the credibility of crystal structures depends heavily on quality control statistics such as R-free that are unreliable when they are computed incorrectly, which they often are when CS is misidentified as special NCS or pseudosymmetry. When mistakes of this kind are made, artificially low values of R-free can give unjustified confidence in the accuracy of the reported structures.