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bioRxiv · 10.1101/331736

Protein design under competition for amino acids availability

Nerattini, F.·Tubiana, L.·Cardelli, C.·Bianco, V.·Dellago, C.·Coluzza, I.
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Abstract

Understanding the origin of the 20 letter alphabet of proteins is a long-lasting biophysical problem. In particular, studies focused extensively on the effect of a reduced alphabet size on the folding properties. However, the natural alphabet is a compromise between versatility and optimisation of the available resources.\n\nHere, for the first time, we include the additional impact of the relative availability of the amino acids. We present a protein design scheme that involves the competition for resources between a protein and a potential interaction partner that, additionally, gives us the chance to investigate the effect of the reduced alphabet on protein-protein interactions. We identify the optimal reduced set of letters for the design of the protein, and we observe that even alphabets reduced down to 4 letters allow for single protein folding. However, it is only with 6 letters that we achieve optimal folding, thus recovering experimental observations.\n\nAdditionally, we notice that the binding between the protein and a potential interaction partner could not be avoided with the investigated reduced alphabets. Therefore, we suggest that aggregation could have been a driving force for the evolution of the large protein alphabet.

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Nerattini, F., Tubiana, L., Cardelli, C., Bianco, V., Dellago, C., Coluzza, I.. 2018-05-25. Protein design under competition for amino acids availability. https://doi.org/10.1101/331736

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