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:	Jacob Bauer, Gabriel Žoldák
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	single-molecule force spectroscopy single-molecule optical trap experiments normal mode analysis computational chemistry Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/800f1fbe92ca470cb165892ab8103d05
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spelling	oai:doaj.org-article:800f1fbe92ca470cb165892ab8103d052021-11-25T18:29:52ZInterpretation of Single-Molecule Force Experiments on Proteins Using Normal Mode Analysis10.3390/nano111127952079-4991https://doaj.org/article/800f1fbe92ca470cb165892ab8103d052021-10-01T00:00:00Zhttps://www.mdpi.com/2079-4991/11/11/2795https://doaj.org/toc/2079-4991Single-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.Jacob BauerGabriel ŽoldákMDPI AGarticlesingle-molecule force spectroscopysingle-molecule optical trap experimentsnormal mode analysiscomputational chemistryChemistryQD1-999ENNanomaterials, Vol 11, Iss 2795, p 2795 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	single-molecule force spectroscopy single-molecule optical trap experiments normal mode analysis computational chemistry Chemistry QD1-999
spellingShingle	single-molecule force spectroscopy single-molecule optical trap experiments normal mode analysis computational chemistry Chemistry QD1-999 Jacob Bauer Gabriel Žoldák Interpretation of Single-Molecule Force Experiments on Proteins Using Normal Mode Analysis
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.
format	article
author	Jacob Bauer Gabriel Žoldák
author_facet	Jacob Bauer Gabriel Žoldák
author_sort	Jacob Bauer
title	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_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_sort	interpretation of single-molecule force experiments on proteins using normal mode analysis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/800f1fbe92ca470cb165892ab8103d05
work_keys_str_mv	AT jacobbauer interpretationofsinglemoleculeforceexperimentsonproteinsusingnormalmodeanalysis AT gabrielzoldak interpretationofsinglemoleculeforceexperimentsonproteinsusingnormalmodeanalysis
_version_	1718411085434847232

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

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