Proteins are the most complex chemicals synthesized in nature and must fold into complicated three-dimensional structures to become active. This poses a particular challenge in explaining their evolution from non-living matter.
So far, efforts to understand protein evolution have focused on domains, independently folding units from which modern proteins are formed. Domains however are themselves too complex to have evolved de novo in an abiotic environment. We think that domains arose from the fusion of shorter, non-folding peptides, which evolved as cofactors supporting a primitive, RNA-based life form (the 'RNA world') .
Computationally, we are trying to reconstruct this ancient peptide set by comparative studies of modern proteins, in the same way in which ancient vocabularies were reconstructed from the comparative study of modern languages. Experimentally, we are exploring how the association of short, non-folding peptide chains may have yielded folded proteins. In particular, we are interested in the role of repetition, a process which is known to have been essential for the emergence of complexity in other biological systems. To this end, we have chosen several structurally repetitive model proteins (Fig. 1,2), which we are studying by means of protein biochemistry and structural biology. We are also interested in several less obviously repetitive domains, particularly in cradle-loop barrels  and β-tent folds .
|Figure 1: β-Propeller||Figure 2: Tetratrico Peptide Repeat (TPR)|
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 Lupas AN., Zhu H., Korycinski M. (2015) The thalidomide-binding domain of cereblon defines the CULT domain family and is a new member
of the β-tent fold. PLoS Comput Biol 11(1):e1004023