DOI: 10.1063/1.1564048. Effects of confinement and crowding on the thermodynamics and kinetics of folding of a minimalist β-barrel protein

Effects of confinement and crowding on the thermodynamics and kinetics of folding of a minimalist β-barrel protein

10.1063/1.1564048

Crossref journal-article

AIP Publishing

The Journal of Chemical Physics (317)

Abstract

We report the results of a molecular dynamics (MD) study of the effects of confinement and molecular crowding on the thermodynamics and kinetics of folding of a 46 residue off-lattice minimalist β-barrel protein. Crowding was mimicked by restricting the protein to a sphere with a soft well repulsive potential. MD simulations were performed on the protein in an unconfined environment, as well as confined to spheres of two different radii, 5.88σ and 11.76σ. Here, σ is the bond length between two adjacent residues and the radius of gyration of the protein in its native state is 2.87σ. We find that for the larger sphere (11.76σ), the folding and collapse temperatures are virtually unchanged from their bulk values, but the average folding time is decreased by 35%. By contrast, the smaller sphere has a much more significant thermodynamic effect (the folding temperature is raised by 28%) but the average folding time is only decreased by 58%. Confinement is also seen to restrict the conformational space accessible to the protein in its denatured state. In addition, confinement appears to change the folding mechanism for this protein, as long-lived intermediates present in the bulk are both modified and have shorter lifetimes when the protein is confined.

Bibliography

Friedel, M., Sheeler, D. J., & Shea, J.-E. (2003). Effects of confinement and crowding on the thermodynamics and kinetics of folding of a minimalist Î²-barrel protein. The Journal of Chemical Physics, 118(17), 8106â8113.

Authors 3

Miriam Friedel (first)
Daniel J. Sheeler (additional)
Joan-Emma Shea (additional)

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Dates

Type	When
Created	22 years, 4 months ago (April 17, 2003, 6:07 p.m.)
Deposited	1 year, 6 months ago (Feb. 7, 2024, 5:11 p.m.)
Indexed	1 year ago (Aug. 26, 2024, 4:26 a.m.)
Issued	22 years, 4 months ago (May 1, 2003)
Published	22 years, 4 months ago (May 1, 2003)
Published Print	22 years, 4 months ago (May 1, 2003)

Funders 0

None

BibTeX

@article{Friedel_2003, title={Effects of confinement and crowding on the thermodynamics and kinetics of folding of a minimalist β-barrel protein}, volume={118}, ISSN={1089-7690}, url={http://dx.doi.org/10.1063/1.1564048}, DOI={10.1063/1.1564048}, number={17}, journal={The Journal of Chemical Physics}, publisher={AIP Publishing}, author={Friedel, Miriam and Sheeler, Daniel J. and Shea, Joan-Emma}, year={2003}, month=may, pages={8106–8113} }

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  "abstract": "<jats:p>We report the results of a molecular dynamics (MD) study of the effects of confinement and molecular crowding on the thermodynamics and kinetics of folding of a 46 residue off-lattice minimalist \u03b2-barrel protein. Crowding was mimicked by restricting the protein to a sphere with a soft well repulsive potential. MD simulations were performed on the protein in an unconfined environment, as well as confined to spheres of two different radii, 5.88\u03c3 and 11.76\u03c3. Here, \u03c3 is the bond length between two adjacent residues and the radius of gyration of the protein in its native state is 2.87\u03c3. We find that for the larger sphere (11.76\u03c3), the folding and collapse temperatures are virtually unchanged from their bulk values, but the average folding time is decreased by 35%. By contrast, the smaller sphere has a much more significant thermodynamic effect (the folding temperature is raised by 28%) but the average folding time is only decreased by 58%. Confinement is also seen to restrict the conformational space accessible to the protein in its denatured state. In addition, confinement appears to change the folding mechanism for this protein, as long-lived intermediates present in the bulk are both modified and have shorter lifetimes when the protein is confined.</jats:p>",
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