Untangling the Complexity of Binding Across Biomolecular Interfaces with Interaction Network Models

The biological functions of large biomolecules such as proteins are often realized through very specific interactions with partner molecules by forming complex protein-protein interaction interfaces. There is a vast amount of pairwise interactions between residues of two proteins as well as water. Residue interaction network (RIN) models are very useful in analyzing the complexity of binding, in particular, when hotspots responsible for molecular recognition are identified with the singular value centrality ( $C^{\mathrm{SV}}$ ) technique, that delivers a single score value per residue quantifying its importance in the binding. The $C^{\mathrm{SV}}$ /RIN methodology is described and its practical usage is illustrated on representative complexes.