Coverage of protein domain families with structural protein-protein interactions: current progress and future trends.

Protein interactions have evolved into highly precise and regulated networks adding an immense layer of complexity to cellular systems. The most accurate atomistic description of protein binding sites can be obtained directly from structures of protein complexes. The availability of structurally characterized protein interfaces significantly improves our understanding of interactomes, and the progress in structural characterization of protein-protein interactions (PPIs) can be measured by calculating the structural coverage of protein domain families. We analyze the coverage of protein domain families (defined according to CDD and Pfam databases) by structures, structural protein-protein complexes and unique protein binding sites. Structural PPI coverage of currently available protein families is about 30% without any signs of saturation in coverage growth dynamics. Given the current growth rates of domain databases and structural PPI deposition, complete domain coverage with PPIs is not expected in the near future. As a result of this study we identify families without any protein-protein interaction evidence (listed on a supporting website http://www.ncbi.nlm.nih.gov/Structure/ibis/coverage/) and propose them as potential targets for structural studies with a focus on protein interactions.

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