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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Nanomaterials |
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| Online Access: | https://www.mdpi.com/2079-4991/11/11/2795 |
| _version_ | 1797509093205737472 |
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| author | Jacob Bauer Gabriel Žoldák |
| author_facet | Jacob Bauer Gabriel Žoldák |
| author_sort | Jacob Bauer |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:13:40Z |
| format | Article |
| id | doaj.art-800f1fbe92ca470cb165892ab8103d05 |
| institution | Directory Open Access Journal |
| issn | 2079-4991 |
| language | English |
| last_indexed | 2024-03-10T05:13:40Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nanomaterials |
| spelling | doaj.art-800f1fbe92ca470cb165892ab8103d052023-11-23T00:38:29ZengMDPI AGNanomaterials2079-49912021-10-011111279510.3390/nano11112795Interpretation of Single-Molecule Force Experiments on Proteins Using Normal Mode AnalysisJacob Bauer0Gabriel Žoldák1Institute of Molecular Biology, Slovak Academy of Sciences, Dúbravská cesta 21, 845 51 Bratislava, SlovakiaCenter for Interdisciplinary Biosciences, P. J. Šafárik University, Technology and Innovation Park, Trieda SNP 1, 041 54 Košice, SlovakiaSingle-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.https://www.mdpi.com/2079-4991/11/11/2795single-molecule force spectroscopysingle-molecule optical trap experimentsnormal mode analysiscomputational chemistry |
| spellingShingle | Jacob Bauer Gabriel Žoldák Interpretation of Single-Molecule Force Experiments on Proteins Using Normal Mode Analysis Nanomaterials single-molecule force spectroscopy single-molecule optical trap experiments normal mode analysis computational chemistry |
| 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 | single-molecule force spectroscopy single-molecule optical trap experiments normal mode analysis computational chemistry |
| url | https://www.mdpi.com/2079-4991/11/11/2795 |
| work_keys_str_mv | AT jacobbauer interpretationofsinglemoleculeforceexperimentsonproteinsusingnormalmodeanalysis AT gabrielzoldak interpretationofsinglemoleculeforceexperimentsonproteinsusingnormalmodeanalysis |