Antibodies recognize and bind their target protein antigens via surface accessible interaction sites, the epitopes (Fig. 35.1), which can involve amino acid side chain and backbone contacts along a linear segment of the antigen amino acid chain (linear epitopes) or which can involve amino acid residues from two or more segments of the protein chain brought together by its folded secondary structure (conformational epitopes). Approaches that systematically study antibody–antigen interactions (AAI) can be directly applied to protein–protein interactions (PPIs) as well and therefore the term epitope is used here in its broadest sense for a protein interaction site and far beyond its default immunological meaning.