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Protein design under competing conditions for the availability of amino acids

Isolating the properties of proteins that allow them to convert sequence into the structure 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 vers...

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Autores principales: Nerattini, Francesca, Tubiana, Luca, Cardelli, Chiara, Bianco, Valentino, Dellago, Christoph, Coluzza, Ivan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021711/
https://www.ncbi.nlm.nih.gov/pubmed/32060385
http://dx.doi.org/10.1038/s41598-020-59401-9
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author Nerattini, Francesca
Tubiana, Luca
Cardelli, Chiara
Bianco, Valentino
Dellago, Christoph
Coluzza, Ivan
author_facet Nerattini, Francesca
Tubiana, Luca
Cardelli, Chiara
Bianco, Valentino
Dellago, Christoph
Coluzza, Ivan
author_sort Nerattini, Francesca
collection PubMed
description Isolating the properties of proteins that allow them to convert sequence into the structure 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. Here, for the first time, we include the impact of the relative availability of the amino acids to extract from the 20 letters the core necessary for protein stability. We present a computational 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 devise a scheme that automatically identifies 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. Additionally, 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 in the evolution of the large protein alphabet.
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spelling pubmed-70217112020-02-24 Protein design under competing conditions for the availability of amino acids Nerattini, Francesca Tubiana, Luca Cardelli, Chiara Bianco, Valentino Dellago, Christoph Coluzza, Ivan Sci Rep Article Isolating the properties of proteins that allow them to convert sequence into the structure 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. Here, for the first time, we include the impact of the relative availability of the amino acids to extract from the 20 letters the core necessary for protein stability. We present a computational 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 devise a scheme that automatically identifies 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. Additionally, 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 in the evolution of the large protein alphabet. Nature Publishing Group UK 2020-02-14 /pmc/articles/PMC7021711/ /pubmed/32060385 http://dx.doi.org/10.1038/s41598-020-59401-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Nerattini, Francesca
Tubiana, Luca
Cardelli, Chiara
Bianco, Valentino
Dellago, Christoph
Coluzza, Ivan
Protein design under competing conditions for the availability of amino acids
title Protein design under competing conditions for the availability of amino acids
title_full Protein design under competing conditions for the availability of amino acids
title_fullStr Protein design under competing conditions for the availability of amino acids
title_full_unstemmed Protein design under competing conditions for the availability of amino acids
title_short Protein design under competing conditions for the availability of amino acids
title_sort protein design under competing conditions for the availability of amino acids
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021711/
https://www.ncbi.nlm.nih.gov/pubmed/32060385
http://dx.doi.org/10.1038/s41598-020-59401-9
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