READING PROTEIN SEQUENCES BACKWARDS

Background: Reading a protein sequence backwards provides a new polype ptide that does not align with its parent sequence. The foldability of this new sequence is questionable. On one hand, structure prediction at low resolution using lattice simulations for such a protein provide d a model close to the native parent fold or to a topological mirror i mage of ii. On the other hand, there is no experimental evidence yet t o tell whether such a retro protein folds (and to which structure) or not. Results: In this work, we have analysed the possibility of a retr o protein folding in two different ways. First, we modelled the retro sequence of the oc-spectrin SH3 domain through distance geometry and m olecular dynamics. This contradicted the plausibility of a mirror imag e of the native domain, whereas basic considerations opposed the likel ihood of the native fold. Second, we obtained experimental evidence th at the retro sequences of the SH3 domain, as well as the B domain of S taphylococcal protein A and the B1 domain of Streptococcal protein G, are unfolded proteins, even though some propensities for the formation of secondary structures might remain. Conclusions: Retro proteins are no more similar to their parent sequences than any random sequence de spite their common hydrophobic/hydrophilic pattern, global amino acid composition and possible tertiary contacts. Although simple folding mo dels contribute to our global understanding of protein folding, they c annot yet be used to predict the structure of new proteins.