Packing bridges in protein crystal structures

On the basis of a statistical analysis of the data deposited in the Protein Data Bank [Berman et al. (2000). Nucleic Acids Res. 28, 235-242; Bernstein et al. (1977). J. Mol. Biol. 112, 535-542], it is shown that two symmetry-related protein molecules are frequently bridged by a small molecule/monoatomic ion, which was used in the crystallization medium despite the fact that it is not a physiological ligand of the macromolecule. It is therefore sensible to suppose that some of the solutes used in crystallizations can favour the nucleation process by bridging and opportunely orienting adjacent protein molecules. This would explain why small changes in the composition of the crystallization solution, for example, the presence of a minor amount of a specific additive, can have a dramatic impact on the outcome of a crystallization experiment.