Automatic inference of protein quaternary structure from crystals

The arrangement of the subunits in an oligomeric protein often cannot be inferred without ambiguity from crystallographic studies. The annotation of the functional assembly of protein structures in the Protein Data Bank (PDB) is incomplete and frequently inconsistent. Instructions for the reconstruction, by symmetry, of the functional assembly from the deposited coordinates are often absent. An automatic procedure is proposed for the inference of assembly structures that are likely to be physiologically relevant. The method scores crystal contacts by their contact size and chemical complementarity. The subunit assembly is then inferred from these scored contacts by a clustering procedure involving a single adjustable parameter. When predicting the oligomeric state for a non-redundant set of 55 monomeric and 163 oligomeric proteins from dimers up to hexamers, a classification error rate of 16% was observed.