Homologous Superfamily: 2.20.25.100

CATH is a tree-like organisation of nodes that begins with the class node (i.e. the first branch-point of the tree) and ends with the domain nodes (i.e. the leaves of the tree). Each node below the class have a parent that they belong to, e.g. the parent of the H level (Homologous superfamily) is the T (Topology). Additionally, each node above the domains have child nodes that belong to them, e.g. the child nodes of a given H (Homologous superfamily) level are the S35 families (domains clustered at > 35% sequence identity).

CATH is a tree-like organisation of nodes that begins with the class node (i.e. the first branch-point of the tree) and ends with the domain nodes (i.e. the leaves of the tree). Each node below the class have a parent that they belong to, e.g. the parent of the H level (Homologous superfamily) is the T (Topology). Additionally, each node above the domains have child nodes that belong to them, e.g. the child nodes of a given H (Homologous superfamily) level are the S35 families (domains clustered at > 35% sequence identity).

The simple answer is that some of the larger superfamilies in CATH comprise relatives which are very structurally diverse, having different secondary structure embellishments. Attempting to provide a global alignment of all domains in the superfamily would result in poor quality alignments. As a result, structural alignments in CATH are generated by first clustering together the structures that have at least some recognisable structural similarity using a normalised RMSD score (SIMAX = RMSDxNumber of residues in the largest domain/number of aligned residues) less than a given cutoff.

A Close Structural Cluster describes a cluster of two or more CATH domains that have been grouped together due to their close structural similarity (SIMAX score < 5Å where SIMAX = RMSD x Number of residues in the larger domain/number of aligned residues).

A Distant Structural Cluster describes a cluster of two or CATH domains that have been grouped together with a more relaxed structural similarity threshold to investigate more distant evolutionary similarities (SIMAX score < 5Å where SIMAX = RMSD x Number of residues in the larger domain/number of aligned residues).

The term "structural neighbour" is used here to describe two CATH domains that share a degree of structural similarity. The SSAP algorithm is used to calculate this similarity and works by generating a structure-based pairwise alignment of the two domains then scoring this alignment using a RMSD score which has been normalised by the length of the larger domain divided by the number of aligned residues (SIMAX).