Nothing about protein structure classification makes sense except in the light of evolution.

In this, the 200th anniversary of Charles Darwin's birth and the 150th anniversary of the publication of the Origin of Species, it is fitting to revisit the classification of protein structures from an evolutionary perspective. Existing classifications use homologous sequence relationships, but knowing that structure is much more conserved that sequence creates an iterative loop from which structures can be further classified beyond that of the domain, thereby teasing out distant evolutionary relationships. The desired classification scheme is then one in which a fold is merely semantics and structure can be classified as either ancestral or derived.