Diffusion, Crowding & Protein Stability in a Dynamic Molecular Model of the Bacterial Cytoplasm
By Sean R. McGuffee, Adrian H. Elcock. PLoS Comput. Biol., 2010
679 citations recorded by the source corpus.
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.
Subfields: Atomic and Molecular Physics, and Optics, Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/a7ec7c64c6090ea6c119e5df8a9aa381e08922a0
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In Atomic and Molecular Physics, and Optics
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Citations in the corpus
- Anomalous transport in the crowded world of biological cells (2013, methodology): “We agree with Elcock [230] that there is clearly a need for theory and simulation of microscopic models that can make qualitative and quantitative predictions of the transport behaviour in crowded environments, at least in vitro.”