Cargando…

Molecular dynamics simulations of membrane proteins under asymmetric ionic concentrations

A computational method is developed to allow molecular dynamics simulations of biomembrane systems under realistic ionic gradients and asymmetric salt concentrations while maintaining the conventional periodic boundary conditions required to minimize finite-size effects in an all-atom explicit solve...

Descripción completa

Detalles Bibliográficos
Autores principales: Khalili-Araghi, Fatemeh, Ziervogel, Brigitte, Gumbart, James C., Roux, Benoît
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3787774/
https://www.ncbi.nlm.nih.gov/pubmed/24081985
http://dx.doi.org/10.1085/jgp.201311014
_version_ 1782286232276959232
author Khalili-Araghi, Fatemeh
Ziervogel, Brigitte
Gumbart, James C.
Roux, Benoît
author_facet Khalili-Araghi, Fatemeh
Ziervogel, Brigitte
Gumbart, James C.
Roux, Benoît
author_sort Khalili-Araghi, Fatemeh
collection PubMed
description A computational method is developed to allow molecular dynamics simulations of biomembrane systems under realistic ionic gradients and asymmetric salt concentrations while maintaining the conventional periodic boundary conditions required to minimize finite-size effects in an all-atom explicit solvent representation. The method, which consists of introducing a nonperiodic energy step acting on the ionic species at the edge of the simulation cell, is first tested with illustrative applications to a simple membrane slab model and a phospholipid membrane bilayer. The nonperiodic energy-step method is then used to calculate the reversal potential of the bacterial porin OmpF, a large cation-specific β-barrel channel, by simulating the I-V curve under an asymmetric 10:1 KCl concentration gradient. The calculated reversal potential of 28.6 mV is found to be in excellent agreement with the values of 26–27 mV measured from lipid bilayer experiments, thereby demonstrating that the method allows realistic simulations of nonequilibrium membrane transport with quantitative accuracy. As a final example, the pore domain of Kv1.2, a highly selective voltage-activated K(+) channel, is simulated in a lipid bilayer under conditions that recreate, for the first time, the physiological K(+) and Na(+) concentration gradients and the electrostatic potential difference of living cells.
format Online
Article
Text
id pubmed-3787774
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-37877742014-04-01 Molecular dynamics simulations of membrane proteins under asymmetric ionic concentrations Khalili-Araghi, Fatemeh Ziervogel, Brigitte Gumbart, James C. Roux, Benoît J Gen Physiol Methods and Approaches A computational method is developed to allow molecular dynamics simulations of biomembrane systems under realistic ionic gradients and asymmetric salt concentrations while maintaining the conventional periodic boundary conditions required to minimize finite-size effects in an all-atom explicit solvent representation. The method, which consists of introducing a nonperiodic energy step acting on the ionic species at the edge of the simulation cell, is first tested with illustrative applications to a simple membrane slab model and a phospholipid membrane bilayer. The nonperiodic energy-step method is then used to calculate the reversal potential of the bacterial porin OmpF, a large cation-specific β-barrel channel, by simulating the I-V curve under an asymmetric 10:1 KCl concentration gradient. The calculated reversal potential of 28.6 mV is found to be in excellent agreement with the values of 26–27 mV measured from lipid bilayer experiments, thereby demonstrating that the method allows realistic simulations of nonequilibrium membrane transport with quantitative accuracy. As a final example, the pore domain of Kv1.2, a highly selective voltage-activated K(+) channel, is simulated in a lipid bilayer under conditions that recreate, for the first time, the physiological K(+) and Na(+) concentration gradients and the electrostatic potential difference of living cells. The Rockefeller University Press 2013-10 /pmc/articles/PMC3787774/ /pubmed/24081985 http://dx.doi.org/10.1085/jgp.201311014 Text en © 2013 Khalili-Araghi et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Methods and Approaches
Khalili-Araghi, Fatemeh
Ziervogel, Brigitte
Gumbart, James C.
Roux, Benoît
Molecular dynamics simulations of membrane proteins under asymmetric ionic concentrations
title Molecular dynamics simulations of membrane proteins under asymmetric ionic concentrations
title_full Molecular dynamics simulations of membrane proteins under asymmetric ionic concentrations
title_fullStr Molecular dynamics simulations of membrane proteins under asymmetric ionic concentrations
title_full_unstemmed Molecular dynamics simulations of membrane proteins under asymmetric ionic concentrations
title_short Molecular dynamics simulations of membrane proteins under asymmetric ionic concentrations
title_sort molecular dynamics simulations of membrane proteins under asymmetric ionic concentrations
topic Methods and Approaches
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3787774/
https://www.ncbi.nlm.nih.gov/pubmed/24081985
http://dx.doi.org/10.1085/jgp.201311014
work_keys_str_mv AT khaliliaraghifatemeh moleculardynamicssimulationsofmembraneproteinsunderasymmetricionicconcentrations
AT ziervogelbrigitte moleculardynamicssimulationsofmembraneproteinsunderasymmetricionicconcentrations
AT gumbartjamesc moleculardynamicssimulationsofmembraneproteinsunderasymmetricionicconcentrations
AT rouxbenoit moleculardynamicssimulationsofmembraneproteinsunderasymmetricionicconcentrations