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Interpretation of Single-Molecule Force Experiments on Proteins Using Normal Mode Analysis

Single-molecule force spectroscopy experiments allow protein folding and unfolding to be explored using mechanical force. Probably the most informative technique for interpreting the results of these experiments at the structural level makes use of steered molecular dynamics (MD) simulations, which...

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Autores principales: Bauer, Jacob, Žoldák, Gabriel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624234/
https://www.ncbi.nlm.nih.gov/pubmed/34835560
http://dx.doi.org/10.3390/nano11112795
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author Bauer, Jacob
Žoldák, Gabriel
author_facet Bauer, Jacob
Žoldák, Gabriel
author_sort Bauer, Jacob
collection PubMed
description Single-molecule force spectroscopy experiments allow protein folding and unfolding to be explored using mechanical force. Probably the most informative technique for interpreting the results of these experiments at the structural level makes use of steered molecular dynamics (MD) simulations, which can explicitly model the protein under load. Unfortunately, this technique is computationally expensive for many of the most interesting biological molecules. Here, we find that normal mode analysis (NMA), a significantly cheaper technique from a computational perspective, allows at least some of the insights provided by MD simulation to be gathered. We apply this technique to three non-homologous proteins that were previously studied by force spectroscopy: T4 lysozyme (T4L), Hsp70 and the glucocorticoid receptor domain (GCR). The NMA results for T4L and Hsp70 are compared with steered MD simulations conducted previously, and we find that we can recover the main results. For the GCR, which did not undergo MD simulation, our approach identifies substructures that correlate with experimentally identified unfolding intermediates. Overall, we find that NMA can make a valuable addition to the analysis toolkit for the structural analysis of single-molecule force experiments on proteins.
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spelling pubmed-86242342021-11-27 Interpretation of Single-Molecule Force Experiments on Proteins Using Normal Mode Analysis Bauer, Jacob Žoldák, Gabriel Nanomaterials (Basel) Article Single-molecule force spectroscopy experiments allow protein folding and unfolding to be explored using mechanical force. Probably the most informative technique for interpreting the results of these experiments at the structural level makes use of steered molecular dynamics (MD) simulations, which can explicitly model the protein under load. Unfortunately, this technique is computationally expensive for many of the most interesting biological molecules. Here, we find that normal mode analysis (NMA), a significantly cheaper technique from a computational perspective, allows at least some of the insights provided by MD simulation to be gathered. We apply this technique to three non-homologous proteins that were previously studied by force spectroscopy: T4 lysozyme (T4L), Hsp70 and the glucocorticoid receptor domain (GCR). The NMA results for T4L and Hsp70 are compared with steered MD simulations conducted previously, and we find that we can recover the main results. For the GCR, which did not undergo MD simulation, our approach identifies substructures that correlate with experimentally identified unfolding intermediates. Overall, we find that NMA can make a valuable addition to the analysis toolkit for the structural analysis of single-molecule force experiments on proteins. MDPI 2021-10-22 /pmc/articles/PMC8624234/ /pubmed/34835560 http://dx.doi.org/10.3390/nano11112795 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bauer, Jacob
Žoldák, Gabriel
Interpretation of Single-Molecule Force Experiments on Proteins Using Normal Mode Analysis
title Interpretation of Single-Molecule Force Experiments on Proteins Using Normal Mode Analysis
title_full Interpretation of Single-Molecule Force Experiments on Proteins Using Normal Mode Analysis
title_fullStr Interpretation of Single-Molecule Force Experiments on Proteins Using Normal Mode Analysis
title_full_unstemmed Interpretation of Single-Molecule Force Experiments on Proteins Using Normal Mode Analysis
title_short Interpretation of Single-Molecule Force Experiments on Proteins Using Normal Mode Analysis
title_sort interpretation of single-molecule force experiments on proteins using normal mode analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624234/
https://www.ncbi.nlm.nih.gov/pubmed/34835560
http://dx.doi.org/10.3390/nano11112795
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