In the preceding chapter, we explored the link between protein structure and function, and showed that the tertiary structure of a protein determines the overall shape of the molecule, the distribution of surface charges and the juxtaposition of critical functional residues. Such residues might constitute the active site of an enzyme, the ligand-binding site of a receptor or the antigen-recognition domain of an antibody. The structure of a protein therefore inﬂuences its function by determining the other molecules with which it can interact and the consequences of those interactions. Protein interactions lie at the heart of most biological processes. Proteins may interact with small molecules, nucleic acids and/or other proteins. Indeed nearly all proteins are gregarious, functioning as part of larger complexes rather than working in isolation. Within such complexes the interactions between proteins may be static or transient, the latter often occurring in signaling and metabolic pathways. From the above it is clear that protein interactions and functions are intimately related, and it follows that the investigation of protein interactions can help in the functional annotation of uncharacterized, hypothetical proteins.