The fundamental unit of protein structure is the domain, defined as a region or regions of a polypeptide that fold independently and possesses a hydrophobic core (see Note 1). Domains, particularly those with enzymatic activities, may possess functions independently of whether they are present in isolation or else part of a larger multidomain protein. Other domains confer regulatory and specificity properties to multidomain proteins usually via the provision of binding sites. Because the majority of eukaryotic proteins, and a large number of eubacterial and archaeal proteins, are multidomain in character, the determination of the structures and functions of these proteins requires detailed consideration of their domain architectures.