"Shallow" knots in which the tail of the polypeptide chain only passes through a loop by a few residues are uncommon, but "deep" knots in which many residues are passed through the loop are extremely rare.

[6] Knottins are small, diverse and stable proteins with important drug design potential.

Inter knottin similarity lies mainly between 20% and 40% sequence identity and 1.5 to 4 A backbone deviations although they all share a tightly knotted disulfide core.

This important variability is likely to arise from the highly diverse loops which connect the successive knotted cysteines.

The prediction of structural models for all knottin sequences would open new directions for the analysis of interaction sites and to provide a better understanding of the structural and functional organization of proteins sharing this scaffold.