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Molecular Dynamics Simulations of a Membrane Protein-Micelle Complex in Vacuo
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
2009 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 131, no 46, 16606-16607 p.Article in journal (Refereed) Published
Abstract [en]

We report the first molecular dynamics simulations of an integral membrane protein in a detergent micelle under vacuum conditions. To mimic the dehydration process in electrospray ionization, the N-terminal outer membrane protein A transmembrane domain (OmpA171) from Escherichia coli embedded in a dodecylphosphocholine (DPC) detergent micelle has been simulated with water shells of varying thickness. Removal of the water molecules leaves the membrane protein relatively unaffected by the vacuum conditions. The major structural change occurs in the surrounding micelle, where the DPC molecules structurally rearrange from a normal-phase micelle with DPC detergents radiating spherically from OmpA171 to a structure where the DPC molecules form a layered onion structure in which the head groups, which strive to interact with each other, form an intermediate layer between the inner layer of tail groups that are expelled to the surface, protruding into the void.

Place, publisher, year, edition, pages
2009. Vol. 131, no 46, 16606-16607 p.
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:uu:diva-127396DOI: 10.1021/ja902962yISI: 000272185400002OAI: oai:DiVA.org:uu-127396DiVA: diva2:329844
Available from: 2010-07-14 Created: 2010-07-13 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Exploring the Molecular Dynamics of Proteins and Viruses
Open this publication in new window or tab >>Exploring the Molecular Dynamics of Proteins and Viruses
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Knowledge about structure and dynamics of the important biological macromolecules — proteins, nucleic acids, lipids and sugars — helps to understand their function. Atomic-resolution structures of macromolecules are routinely captured with X-ray crystallography and other techniques. In this thesis, simulations are used to explore the dynamics of the molecules beyond the static structures.

Viruses are machines constructed from macromolecules. Crystal structures of them reveal little to no information about their genomes. In simulations of empty capsids, we observed a correlation between the spatial distribution of chloride ions in the solution and the position of RNA in crystals of satellite tobacco necrosis virus (STNV) and satellite tobacco mosaic virus (STMV). In this manner, structural features of the non-symmetric RNA could also be inferred.

The capsid of STNV binds calcium ions on the icosahedral symmetry axes. The release of these ions controls the activation of the virus particle upon infection. Our simulations reproduced the swelling of the capsid upon removal of the ions and we quantified the water permeability of the capsid. The structure and dynamics of the expanded capsid suggest that the disassembly is initiated at the 3-fold symmetry axis.

Several experimental methods require biomolecular samples to be injected into vacuum, such as mass-spectrometry and diffractive imaging of single particles. It is therefore important to understand how proteins and molecule-complexes respond to being aerosolized. In simulations we mimicked the dehydration process upon going from solution into the gas phase. We find that two important factors for structural stability of proteins are the temperature and the level of residual hydration. The simulations support experimental claims that membrane proteins can be protected by a lipid micelle and that a non-membrane protein could be stabilized in a reverse micelle in the gas phase. A water-layer around virus particles would impede the signal in diffractive experiments, but our calculations estimate that it should be possible to determine the orientation of the particle in individual images, which is a prerequisite for three-dimensional reconstruction.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 45 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 919
Keyword
molecular dynamics, virus dynamics, capsid dissolution, satellite tobacco necrosis virus, satellite tobacco mosaic virus, virus genome structure, gas phase protein structure, water layer, micelle embedded protein, membrane protein
National Category
Biological Sciences Biochemistry and Molecular Biology Biophysics Structural Biology
Research subject
Chemistry with specialization in Biophysics
Identifiers
urn:nbn:se:uu:diva-172284 (URN)978-91-554-8335-7 (ISBN)
Public defence
2012-05-25, B41, Uppsala Biomedicinska Centrum, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Note
BMC B41, 25/5, 9:15Available from: 2012-05-04 Created: 2012-04-03 Last updated: 2012-08-01Bibliographically approved

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Larsson, Daniel S. D.van der Spoel, David

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