About - ProSwap - Wodak Lab

ProSwap allows you to identify and visualize the swapped segments of intertwined proteins and 3D Domain-Swapped structures. Intertwined proteins are homomeric assemblies of polypeptide chains that appear ‘tangled’ or ‘swapped’. These proteins have a high number of intermolecular associations, and therefore may be the underlying cause of protein misfolding and amyloid formation. Intertwined proteins are known to aggregate in humans, leading to several neurodegenerative diseases.

To investigate the swapped features of known proteins, submit a set of PDB identifiers via the search tab. ProSwap will then return a list of homomeric subunit-subunit associations, or ‘interfaces’, found among the provided structures. These results may include swapped and/or non-swapped interfaces. Swapped interfaces can be identified by the presence of a RIAD value. Each interface can then be examined in detail by following the provided link.


Interface: homomeric subunit-subunit associations. All interfaces are classified into one of three symmetrical categories:

  • Dimeric interfaces have a twofold rotational symmetry.
  • Oligomeric interfaces have three-fold or higher rotational symmetry.
  • Polymeric interfaces propagate along the screw axis of a crystal lattice.

Non-Contiguous Structural Domain (NCSD): a compact substructure of a macromolecular assembly. For non-intertwined proteins, the NCSDs correspond to individual subunits. When polypeptide chains are intertwined, intermolecular NCSDs are formed. These NCSDs consist of the swapped residues from one subunit and the non-swapped residues of a second subunit.

Swap: a set of residues along a polypeptide chain that form compact, intermolecular associations with a neighboring subunit. A swap may be S-type or D-type. D-type swaps correspond to discrete structural domains as defined by CATH. The remainder are swapped segments, or S-type.

Subunit Interface Area (SIA): the solvent accessible surface area buried between two polypeptide chains.

NCSD Interface Area (NIA): is the solvent accessible surface area buried between two NCSDs.

Relative Interface Area Difference (RIAD): describes the extent of swapping. The scale ranges from 0 to 1. Smaller numbers represent more subtle swaps while larger values reflect more obvious swapped structures. The RIAD value is given by the formula: RIAD = ( SIA – NIA ) / SIA