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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....

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Detalles Bibliográficos
Autores principales: Maffeo, Christopher, Chou, Han-Yi, Aksimentiev, Aleksei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
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.
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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
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