Analysis of Complex Networks

9.5 Identification of Macromolecular Assemblies in Crystal Packing

The biochemical functions of many proteins are dependent on their ability to form complexes. The way in which protein chains assemble in a complex represents the protein quaternary structure (PQS). Experimental identification of PQS is a complicated procedure that normally involves use of several complementing techniques, such as mobility and mass measurements [86, 87], light scattering [86], neutron and X-ray scattering [88, 89], nuclear magnetic resonance [90], electron microscopy [91], and others. However, most protein structure data (80% of the PDB) come from experiments on X-ray diffraction on macromolecular crystals [92]. It is reasonable to expect that stable protein complexes do not change during crystallization, and therefore they should be identifiable in crystal packing.

The inference of PQS from crystallographic data is not a straightforward procedure. A complex may be represented as a graph, where vertices are protein chains and edges are interchain interfaces that bind chains together. The binding force of interfaces comes from hydrophobic interactions [93, 94] and weak bonds, such as hydrogen bonds, salt bridges, and disulphide bonds [94–96]. There is no obvious way, in general, to discriminate between inter- and intracomplex interfaces. Numerous attempts to find a set of discriminating parameters have had limited success [97–99].

Chemically, a complex represents a stable structure if its free Gibbs ...