The CATH database

The number of solved protein structures is increasing at an exceptional rate. At the time of writing, the Protein Data Bank[1,2] (PDB) contains more than 61,000 structures. The CATH database[3,4] is a classification of protein domains (sub-sequences of proteins that may fold, evolve and function independently of the rest of the protein), based not only on sequence information, but also on structural and functional properties. CATH offers an important tool to researchers, as proteins with even very little sequence similarity often are both structurally and functionally related[5].The most recent version of CATH (version 3.2.0, released July 2008[6]) contains 114,215 domains, classified in a hierarchical scheme with four main levels (listed from the top and down) called class (C), architecture (A), topology (T) and homologous superfamily (H) -- hence the name CATH. More than 20,000 domains have been added since the previous release (version 3.1.0, January 2007), and the rate of new additions is expected to increase. (The first CATH release[3] from 1997 contained only 8,078 domains.)At the C-level, domains are grouped according to their secondary structure content into four categories: mainly alpha, mainly beta, mixed alpha-beta; and a fourth category which contains domains with only few secondary structures. The A-level groups domains according to the general orientations of their secondary structures. At the T-level, the connectivity (ie the order) of the secondary structures is taken into account. The grouping of domains at the H-level is based on a combination of both sequence similarity and a measure of structural similarity obtained from the dynamic programming algorithm SSAP[7]. To supplement the traditional alignment of the α-carbon atoms of the protein backbone, SSAP gains additional strength by also aligning β-carbon atoms of the amino acid side chains and thus also takes into account the rotational conformation of the protein chains.In addition to the four m