Inference of Macromolecular Assemblies from Crystalline State

We discuss basic physical–chemical principles underlying the formation of stable macromolecular complexes, which in many cases are likely to be the biological units performing a certain physiological function. We also consider available theoretical approaches to the calculation of macromolecular affinity and entropy of complexation. The latter is shown to play an important role and make a major effect on complex size and symmetry. We develop a new method, based on chemical thermodynamics, for automatic detection of macromolecular assemblies in the Protein Data Bank (PDB) entries that are the results of X-ray diffraction experiments. As found, biological units may be recovered at 80–90% success rate, which makes X-ray crystallography an important source of experimental data on macromolecular complexes and protein–protein interactions. The method is implemented as a public WWW service†.