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Single-molecule biophysics experiments in silico: Toward a physical model of a replisome
The interpretation of single-molecule experiments is frequently aided by computational modeling of biomolecular dynamics. The growth of computing power and ongoing validation of computational models suggest that it soon may be possible to replace some experiments outright with computational mimics....
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9062759/ https://www.ncbi.nlm.nih.gov/pubmed/35521518 http://dx.doi.org/10.1016/j.isci.2022.104264 |
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author | Maffeo, Christopher Chou, Han-Yi Aksimentiev, Aleksei |
author_facet | Maffeo, Christopher Chou, Han-Yi Aksimentiev, Aleksei |
author_sort | Maffeo, Christopher |
collection | PubMed |
description | The interpretation of single-molecule experiments is frequently aided by computational modeling of biomolecular dynamics. The growth of computing power and ongoing validation of computational models suggest that it soon may be possible to replace some experiments outright with computational mimics. Here, we offer a blueprint for performing single-molecule studies in silico using a DNA-binding protein as a test bed. We demonstrate how atomistic simulations, typically limited to sub-millisecond durations and zeptoliter volumes, can guide development of a coarse-grained model for use in simulations that mimic single-molecule experiments. We apply the model to recapitulate, in silico, force-extension characterization of protein binding to single-stranded DNA and protein and DNA replacement assays, providing a detailed portrait of the underlying mechanics. Finally, we use the model to simulate the trombone loop of a replication fork, a large complex of proteins and DNA. |
format | Online Article Text |
id | pubmed-9062759 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-90627592022-05-04 Single-molecule biophysics experiments in silico: Toward a physical model of a replisome Maffeo, Christopher Chou, Han-Yi Aksimentiev, Aleksei iScience Article The interpretation of single-molecule experiments is frequently aided by computational modeling of biomolecular dynamics. The growth of computing power and ongoing validation of computational models suggest that it soon may be possible to replace some experiments outright with computational mimics. Here, we offer a blueprint for performing single-molecule studies in silico using a DNA-binding protein as a test bed. We demonstrate how atomistic simulations, typically limited to sub-millisecond durations and zeptoliter volumes, can guide development of a coarse-grained model for use in simulations that mimic single-molecule experiments. We apply the model to recapitulate, in silico, force-extension characterization of protein binding to single-stranded DNA and protein and DNA replacement assays, providing a detailed portrait of the underlying mechanics. Finally, we use the model to simulate the trombone loop of a replication fork, a large complex of proteins and DNA. Elsevier 2022-04-18 /pmc/articles/PMC9062759/ /pubmed/35521518 http://dx.doi.org/10.1016/j.isci.2022.104264 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Maffeo, Christopher Chou, Han-Yi Aksimentiev, Aleksei Single-molecule biophysics experiments in silico: Toward a physical model of a replisome |
title | Single-molecule biophysics experiments in silico: Toward a physical model of a replisome |
title_full | Single-molecule biophysics experiments in silico: Toward a physical model of a replisome |
title_fullStr | Single-molecule biophysics experiments in silico: Toward a physical model of a replisome |
title_full_unstemmed | Single-molecule biophysics experiments in silico: Toward a physical model of a replisome |
title_short | Single-molecule biophysics experiments in silico: Toward a physical model of a replisome |
title_sort | single-molecule biophysics experiments in silico: toward a physical model of a replisome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9062759/ https://www.ncbi.nlm.nih.gov/pubmed/35521518 http://dx.doi.org/10.1016/j.isci.2022.104264 |
work_keys_str_mv | AT maffeochristopher singlemoleculebiophysicsexperimentsinsilicotowardaphysicalmodelofareplisome AT chouhanyi singlemoleculebiophysicsexperimentsinsilicotowardaphysicalmodelofareplisome AT aksimentievaleksei singlemoleculebiophysicsexperimentsinsilicotowardaphysicalmodelofareplisome |