Passive Transmembrane Permeation Mechanisms of Monovalent Ions Explored by Molecular Dynamics Simulations

Hui Yuan Zhang, Qin Xu, Yu Kun Wang, Tang Zhen Zhao, Dan Hu, Dong Qing Wei

    Research output: Contribution to journalArticle

    Abstract

    Passive or unassisted ion permeation through lipid bilayers involves a type of rare events by which cells regulate their salt concentrations and pH. It is important to understand its mechanism in order to develop technologies of, for example, delivering or maintaining small drug-like molecules inside cells. In earlier simulations of passive ion permeations, the commonly used sampling methods usually define the positions of ions relative to the membrane as a measure of permeation, i.e., the collective variable, ignoring the active participations of other particles. Newly defined collective variables involving the movements of ions, lipids, and water molecules allow us to identify the transition paths on the free energy landscape using the 2D umbrella sampling techniques. In this work, this technique was used to study the permeation processes of some well-known ions, sodium, potassium, and chloride. It is found permeations of sodium and potassium are assisted by important lipid bilayer deformations and massive water solvation, while chloride may not. Chloride may have two different possible pathways, in which the energetic favorable one is similar to the solubility-diffusion model. The free energy barriers for the permeation of these ions are in semiquantitative agreement with experiments. Further analyses on the distributions of oxygens and interaction energies suggest the electrostatic interactions between ions and polar headgroups of lipids may greatly influence membrane deformation as well as the water wire and furthermore the free energy barriers of waterwire mediated pathways. For chloride, the nonwaterwire pathway may be energetically favorable.

    Original languageEnglish (US)
    Pages (from-to)4959-4969
    Number of pages11
    JournalJournal of Chemical Theory and Computation
    Volume12
    Issue number10
    DOIs
    StatePublished - Oct 11 2016

    Fingerprint

    Permeation
    Molecular dynamics
    Ions
    molecular dynamics
    Computer simulation
    lipids
    chlorides
    ions
    Free energy
    simulation
    Chlorides
    Lipid bilayers
    Energy barriers
    free energy
    Lipids
    Potassium
    Water
    potassium
    Sodium
    sampling

    ASJC Scopus subject areas

    • Computer Science Applications
    • Physical and Theoretical Chemistry

    Cite this

    Passive Transmembrane Permeation Mechanisms of Monovalent Ions Explored by Molecular Dynamics Simulations. / Zhang, Hui Yuan; Xu, Qin; Wang, Yu Kun; Zhao, Tang Zhen; Hu, Dan; Wei, Dong Qing.

    In: Journal of Chemical Theory and Computation, Vol. 12, No. 10, 11.10.2016, p. 4959-4969.

    Research output: Contribution to journalArticle

    Zhang, Hui Yuan ; Xu, Qin ; Wang, Yu Kun ; Zhao, Tang Zhen ; Hu, Dan ; Wei, Dong Qing. / Passive Transmembrane Permeation Mechanisms of Monovalent Ions Explored by Molecular Dynamics Simulations. In: Journal of Chemical Theory and Computation. 2016 ; Vol. 12, No. 10. pp. 4959-4969.
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