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Diffusion, Crowding & Protein Stability in a Dynamic Molecular Model of the Bacterial Cytoplasm

A longstanding question in molecular biology is the extent to which the behavior of macromolecules observed in vitro accurately reflects their behavior in vivo. A number of sophisticated experimental techniques now allow the behavior of individual types of macromolecule to be studied directly in viv...

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Detalles Bibliográficos
Autores principales: McGuffee, Sean R., Elcock, Adrian H.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2832674/
https://www.ncbi.nlm.nih.gov/pubmed/20221255
http://dx.doi.org/10.1371/journal.pcbi.1000694
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author McGuffee, Sean R.
Elcock, Adrian H.
author_facet McGuffee, Sean R.
Elcock, Adrian H.
author_sort McGuffee, Sean R.
collection PubMed
description A longstanding question in molecular biology is the extent to which the behavior of macromolecules observed in vitro accurately reflects their behavior in vivo. A number of sophisticated experimental techniques now allow the behavior of individual types of macromolecule to be studied directly in vivo; none, however, allow a wide range of molecule types to be observed simultaneously. In order to tackle this issue we have adopted a computational perspective, and, having selected the model prokaryote Escherichia coli as a test system, have assembled an atomically detailed model of its cytoplasmic environment that includes 50 of the most abundant types of macromolecules at experimentally measured concentrations. Brownian dynamics (BD) simulations of the cytoplasm model have been calibrated to reproduce the translational diffusion coefficients of Green Fluorescent Protein (GFP) observed in vivo, and “snapshots” of the simulation trajectories have been used to compute the cytoplasm's effects on the thermodynamics of protein folding, association and aggregation events. The simulation model successfully describes the relative thermodynamic stabilities of proteins measured in E. coli, and shows that effects additional to the commonly cited “crowding” effect must be included in attempts to understand macromolecular behavior in vivo.
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spelling pubmed-28326742010-03-11 Diffusion, Crowding & Protein Stability in a Dynamic Molecular Model of the Bacterial Cytoplasm McGuffee, Sean R. Elcock, Adrian H. PLoS Comput Biol Research Article A longstanding question in molecular biology is the extent to which the behavior of macromolecules observed in vitro accurately reflects their behavior in vivo. A number of sophisticated experimental techniques now allow the behavior of individual types of macromolecule to be studied directly in vivo; none, however, allow a wide range of molecule types to be observed simultaneously. In order to tackle this issue we have adopted a computational perspective, and, having selected the model prokaryote Escherichia coli as a test system, have assembled an atomically detailed model of its cytoplasmic environment that includes 50 of the most abundant types of macromolecules at experimentally measured concentrations. Brownian dynamics (BD) simulations of the cytoplasm model have been calibrated to reproduce the translational diffusion coefficients of Green Fluorescent Protein (GFP) observed in vivo, and “snapshots” of the simulation trajectories have been used to compute the cytoplasm's effects on the thermodynamics of protein folding, association and aggregation events. The simulation model successfully describes the relative thermodynamic stabilities of proteins measured in E. coli, and shows that effects additional to the commonly cited “crowding” effect must be included in attempts to understand macromolecular behavior in vivo. Public Library of Science 2010-03-05 /pmc/articles/PMC2832674/ /pubmed/20221255 http://dx.doi.org/10.1371/journal.pcbi.1000694 Text en McGuffee, Elcock. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
McGuffee, Sean R.
Elcock, Adrian H.
Diffusion, Crowding & Protein Stability in a Dynamic Molecular Model of the Bacterial Cytoplasm
title Diffusion, Crowding & Protein Stability in a Dynamic Molecular Model of the Bacterial Cytoplasm
title_full Diffusion, Crowding & Protein Stability in a Dynamic Molecular Model of the Bacterial Cytoplasm
title_fullStr Diffusion, Crowding & Protein Stability in a Dynamic Molecular Model of the Bacterial Cytoplasm
title_full_unstemmed Diffusion, Crowding & Protein Stability in a Dynamic Molecular Model of the Bacterial Cytoplasm
title_short Diffusion, Crowding & Protein Stability in a Dynamic Molecular Model of the Bacterial Cytoplasm
title_sort diffusion, crowding & protein stability in a dynamic molecular model of the bacterial cytoplasm
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2832674/
https://www.ncbi.nlm.nih.gov/pubmed/20221255
http://dx.doi.org/10.1371/journal.pcbi.1000694
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