Abstract
The increasing amount of structural information on protein-protein interactions makes it possible to predict the structure of protein-protein complexes by comparison/alignment of the interacting proteins to the ones in cocrystallized complexes. In the predictions based on structure similarity, the template search is performed by structural alignment of the target interactors with the entire structures or with the interface only of the subunits in cocrystallized complexes. This study investigates the scope of the structural similarity that facilitates the detection of a broad range of templates significantly divergent from the targets. The analysis of the target-template similarity is based on models of protein-protein complexes in a large representative set of heterodimers. The similarity of the biological and crystal packing interfaces, dissimilar interface structural motifs in overall similar structures, interface similarity to the full structure, and local similarity away from the interface were analyzed. The structural similarity at the protein-protein interfaces only was observed in ~25% of target-template pairs with sequence identity <20% and primarily homodimeric templates. For ~50% of the target-template pairs, the similarity at the interface was accompanied by the similarity of the whole structure. However, the structural similarity at the interfaces was still stronger than that of the noninterface parts. The study provides insights into structural and functional diversity of protein-protein complexes, and relative performance of the interface and full structure alignment in docking.