The SISYPHUS alignments are grouped into three categories:

Fragment alignment category

The multiple alignments belonging to this category contain contiguous or non-contiguous protein fragments that can be distinguish by a well defined set of functional or structural properties. The structural regions included in the alignments are local substructures which lack compactness and a hydrophobic core. These local substructures usually comprise a short stretch of amino acid residues (~20-50 aa) and often display a substantial structural, sequence and functional similarity. Frequently, fragments represent internal structural repeats or similar structural motifs in globally distinct protein structure

Homologous alignment category

The structural alignments of this category consist of proteins in which similar functional and/or structural features suggest a common evolutionary origin. The structural regions included in the alignments are compact substructures composed of one or more segments of polypeptide chain, the entire polypeptide chain or several polypeptide chains. The multiple alignments of this category provide a structural evidence for the relationships between proteins with various topological rearrangements such as circular permutation, segment-swapping, etc.The rearrangement of the secondary structural elements in these proteins may reflect an evolutionary event.

Fold alignment category

The alignments of this category contain protein regions in which core elements are topologically similar, have a structurally equivalent counterpart and contain specific or unusual features. Their peripheral structural elements can differ substantially. The regions included in the alignments may come from evolutionary unrelated proteins. Their structural similarity arises from the physics and chemistry of proteins that favors certain packing arrangements.