Diffusion, crowding & protein stability in a dynamic molecular model of the bacterial cytoplasm

Sean R McGuffee; Adrian H Elcock

doi:10.1371/journal.pcbi.1000694

Back

Diffusion, crowding & protein stability in a dynamic molecular model of the bacterial cytoplasm

Journal article

Open access

Diffusion, crowding & protein stability in a dynamic molecular model of the bacterial cytoplasm

Sean R McGuffee and Adrian H Elcock

PLoS computational biology, Vol.6(3), pp.e1000694-e1000694

03/05/2010

DOI: 10.1371/journal.pcbi.1000694

PMCID: PMC2832674

PMID: 20221255

Files and links (1)

url

https://doi.org/10.1371/journal.pcbi.1000694View

Published (Version of record) Open Access

Abstract

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.

Cytoplasm - chemistry

Models, Chemical

Computer Simulation

Models, Molecular

Protein Conformation

Escherichia coli - chemistry

Escherichia coli Proteins - chemistry

Protein Folding

Details

Title: Subtitle: Diffusion, crowding & protein stability in a dynamic molecular model of the bacterial cytoplasm
Creators: Sean R McGuffee - Department of Biochemistry, University of Iowa, Iowa City, Iowa, United States of America
Adrian H Elcock
Resource Type: Journal article
Publication Details: PLoS computational biology, Vol.6(3), pp.e1000694-e1000694
DOI: 10.1371/journal.pcbi.1000694
PMID: 20221255
PMCID: PMC2832674
NLM abbreviation: PLoS Comput Biol
ISSN: 1553-734X
eISSN: 1553-7358
Publisher: United States
Language: English
Date published: 03/05/2010
Academic Unit: Physics and Astronomy; Biochemistry and Molecular Biology
Record Identifier: 9984024414302771

Metrics

18 Record Views

598 Times Cited - Web of Science