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Linking protein structural and functional change to mutation using amino acid networks
The function of a protein is strongly dependent on its structure. During evolution, proteins acquire new functions through mutations in the amino-acid sequence. Given the advance in deep mutational scanning, recent findings have found functional change to be position dependent, notwithstanding the c...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8782487/ https://www.ncbi.nlm.nih.gov/pubmed/35061689 http://dx.doi.org/10.1371/journal.pone.0261829 |
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author | Sotomayor-Vivas, Cristina Hernández-Lemus, Enrique Dorantes-Gilardi, Rodrigo |
author_facet | Sotomayor-Vivas, Cristina Hernández-Lemus, Enrique Dorantes-Gilardi, Rodrigo |
author_sort | Sotomayor-Vivas, Cristina |
collection | PubMed |
description | The function of a protein is strongly dependent on its structure. During evolution, proteins acquire new functions through mutations in the amino-acid sequence. Given the advance in deep mutational scanning, recent findings have found functional change to be position dependent, notwithstanding the chemical properties of mutant and mutated amino acids. This could indicate that structural properties of a given position are potentially responsible for the functional relevance of a mutation. Here, we looked at the relation between structure and function of positions using five proteins with experimental data of functional change available. In order to measure structural change, we modeled mutated proteins via amino-acid networks and quantified the perturbation of each mutation. We found that structural change is position dependent, and strongly related to functional change. Strong changes in protein structure correlate with functional loss, and positions with functional gain due to mutations tend to be structurally robust. Finally, we constructed a computational method to predict functionally sensitive positions to mutations using structural change that performs well on all five proteins with a mean precision of 74.7% and recall of 69.3% of all functional positions. |
format | Online Article Text |
id | pubmed-8782487 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-87824872022-01-22 Linking protein structural and functional change to mutation using amino acid networks Sotomayor-Vivas, Cristina Hernández-Lemus, Enrique Dorantes-Gilardi, Rodrigo PLoS One Research Article The function of a protein is strongly dependent on its structure. During evolution, proteins acquire new functions through mutations in the amino-acid sequence. Given the advance in deep mutational scanning, recent findings have found functional change to be position dependent, notwithstanding the chemical properties of mutant and mutated amino acids. This could indicate that structural properties of a given position are potentially responsible for the functional relevance of a mutation. Here, we looked at the relation between structure and function of positions using five proteins with experimental data of functional change available. In order to measure structural change, we modeled mutated proteins via amino-acid networks and quantified the perturbation of each mutation. We found that structural change is position dependent, and strongly related to functional change. Strong changes in protein structure correlate with functional loss, and positions with functional gain due to mutations tend to be structurally robust. Finally, we constructed a computational method to predict functionally sensitive positions to mutations using structural change that performs well on all five proteins with a mean precision of 74.7% and recall of 69.3% of all functional positions. Public Library of Science 2022-01-21 /pmc/articles/PMC8782487/ /pubmed/35061689 http://dx.doi.org/10.1371/journal.pone.0261829 Text en © 2022 Sotomayor-Vivas et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Sotomayor-Vivas, Cristina Hernández-Lemus, Enrique Dorantes-Gilardi, Rodrigo Linking protein structural and functional change to mutation using amino acid networks |
title | Linking protein structural and functional change to mutation using amino acid networks |
title_full | Linking protein structural and functional change to mutation using amino acid networks |
title_fullStr | Linking protein structural and functional change to mutation using amino acid networks |
title_full_unstemmed | Linking protein structural and functional change to mutation using amino acid networks |
title_short | Linking protein structural and functional change to mutation using amino acid networks |
title_sort | linking protein structural and functional change to mutation using amino acid networks |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8782487/ https://www.ncbi.nlm.nih.gov/pubmed/35061689 http://dx.doi.org/10.1371/journal.pone.0261829 |
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