ABSTRACT

In recent years, many aspects of biology have been likened to networks, in which distinct nodes (e.g., cells or molecules) can be defined that interact with one another within a system to perform various biological functions. While networks have most commonly been invoked to describe large, organismal level systems, they have also found some traction in illustrating the ways in which proteins interact with one another. Network maps have been constructed to depict all of the possible protein-protein interactions within a cell (e.g., the interactome), essentially a low-resolution view of molecular recognition. At higher resolution, thinking of protein-protein binding sites as networks of amino acid residues that communicate with one another both structurally and energetically has begun to reveal how the modular architecture of protein interfaces and the networked communications within them serve as driving forces for protein complex specificity and affinity. Studies aimed at defining the biophysical basis of these communication events within protein-protein binding sites may serve as an experimental foundation for improving algorithms designed to predict proteinprotein interactions.