Matches in SemOpenAlex for { <https://semopenalex.org/work/W3122864963> ?p ?o ?g. }
- W3122864963 endingPage "1035" @default.
- W3122864963 startingPage "1020" @default.
- W3122864963 abstract "Different mechanisms have been proposed to explain the permeation of charged compounds through lipid membranes. Overall, it is expected that an ion-induced defect permeation mechanism, where substantial membrane deformations accompany ion movement, should be dominant in thin membranes but that a solubility–diffusion mechanism, where ions partition into the membrane core with large associated dehydration energy costs, becomes dominant in thicker membranes. However, while this physical picture is intuitively reasonable, capturing the interconversion between these two permeation mechanisms in molecular dynamics (MD) simulations based on atomic models is challenging. In particular, simulations relying on nonpolarizable force fields are artificially unfavorable to the solubility–diffusion mechanism, as induced polarization of the nonpolar hydrocarbon is ignored, causing overestimated free energy costs for charged molecules to enter into this region of the membrane. In this study, all-atom MD simulations based on nonpolarizable and polarizable force fields are used to quantitatively characterize the permeation process for the arginine side chain analog methyl-guanidinium through bilayer membranes of mono-unsaturated phosphatidylcholine lipids with and without cholesterol, resulting in thicknesses spanning from ∼24 to ∼42 Å. With simulations based on a nonpolarizable force field, ion translocation can take place solely through an ion-induced defect mechanism, with free energy barriers increasing linearly from 14 to 40 kcal/mol, depending on the thickness. However, with simulations based on a polarizable force field, ion translocation is predominantly dominated by an ion-induced defect mechanism in thin membranes, which progressively converts to a solubility–diffusion mechanism as the membranes get thicker. The transition between the two mechanisms occurs at a thickness of ∼29 Å, with lipid tails of 22 or more carbon atoms. This situation appears to represent the upper limit for ion-induced defect permeation within the current polarizable models. Beyond this thickness, it becomes energetically preferable for the ion to dehydrate and partition into the membrane core—a phenomenon that cannot be captured using the nonpolarizable models. Induced electronic polarizability therefore leads not just to a shift in permeation energetics but to an interconversion between two strikingly different physical mechanisms. The result highlights the importance of induced polarizability in modeling lipid membranes." @default.
- W3122864963 created "2021-02-01" @default.
- W3122864963 creator A5031310158 @default.
- W3122864963 creator A5034111252 @default.
- W3122864963 creator A5068923509 @default.
- W3122864963 creator A5080873196 @default.
- W3122864963 date "2021-01-25" @default.
- W3122864963 modified "2023-10-15" @default.
- W3122864963 title "Molecular Dynamics Simulations Based on Polarizable Models Show that Ion Permeation Interconverts between Different Mechanisms as a Function of Membrane Thickness" @default.
- W3122864963 cites W1106171373 @default.
- W3122864963 cites W1952317074 @default.
- W3122864963 cites W1964810993 @default.
- W3122864963 cites W1965467605 @default.
- W3122864963 cites W1967088448 @default.
- W3122864963 cites W1967360315 @default.
- W3122864963 cites W1972758026 @default.
- W3122864963 cites W1975818743 @default.
- W3122864963 cites W1976484542 @default.
- W3122864963 cites W1976499671 @default.
- W3122864963 cites W1980963182 @default.
- W3122864963 cites W1984014838 @default.
- W3122864963 cites W1984456841 @default.
- W3122864963 cites W1985309426 @default.
- W3122864963 cites W1987877181 @default.
- W3122864963 cites W1989784389 @default.
- W3122864963 cites W1989868560 @default.
- W3122864963 cites W1989998611 @default.
- W3122864963 cites W1990451546 @default.
- W3122864963 cites W1991794210 @default.
- W3122864963 cites W1992690229 @default.
- W3122864963 cites W1993177346 @default.
- W3122864963 cites W1993692047 @default.
- W3122864963 cites W1994197757 @default.
- W3122864963 cites W1995159519 @default.
- W3122864963 cites W1995229360 @default.
- W3122864963 cites W1996420136 @default.
- W3122864963 cites W1996795941 @default.
- W3122864963 cites W1998359737 @default.
- W3122864963 cites W1998672634 @default.
- W3122864963 cites W1999077168 @default.
- W3122864963 cites W2000584624 @default.
- W3122864963 cites W2000775586 @default.
- W3122864963 cites W2000998941 @default.
- W3122864963 cites W2010471143 @default.
- W3122864963 cites W2015344098 @default.
- W3122864963 cites W2015835531 @default.
- W3122864963 cites W2016343967 @default.
- W3122864963 cites W2017196167 @default.
- W3122864963 cites W2017544790 @default.
- W3122864963 cites W2019036104 @default.
- W3122864963 cites W2019657469 @default.
- W3122864963 cites W2020405150 @default.
- W3122864963 cites W2021125439 @default.
- W3122864963 cites W2022072508 @default.
- W3122864963 cites W2027296812 @default.
- W3122864963 cites W2027408247 @default.
- W3122864963 cites W2028138612 @default.
- W3122864963 cites W2030143885 @default.
- W3122864963 cites W2030487072 @default.
- W3122864963 cites W2031430636 @default.
- W3122864963 cites W2035423970 @default.
- W3122864963 cites W2037773086 @default.
- W3122864963 cites W2038581484 @default.
- W3122864963 cites W2038758364 @default.
- W3122864963 cites W2043429268 @default.
- W3122864963 cites W2047836608 @default.
- W3122864963 cites W2048550135 @default.
- W3122864963 cites W2048623371 @default.
- W3122864963 cites W2051221402 @default.
- W3122864963 cites W2054342311 @default.
- W3122864963 cites W2054598006 @default.
- W3122864963 cites W2054602599 @default.
- W3122864963 cites W2055425528 @default.
- W3122864963 cites W2055592362 @default.
- W3122864963 cites W2056232124 @default.
- W3122864963 cites W2056296879 @default.
- W3122864963 cites W2057653269 @default.
- W3122864963 cites W2058107268 @default.
- W3122864963 cites W2058321810 @default.
- W3122864963 cites W2060366601 @default.
- W3122864963 cites W2061969981 @default.
- W3122864963 cites W2062092582 @default.
- W3122864963 cites W2064761355 @default.
- W3122864963 cites W2065464482 @default.
- W3122864963 cites W2066414494 @default.
- W3122864963 cites W2067174909 @default.
- W3122864963 cites W2068636421 @default.
- W3122864963 cites W2069737049 @default.
- W3122864963 cites W2071475257 @default.
- W3122864963 cites W2072738851 @default.
- W3122864963 cites W2073778787 @default.
- W3122864963 cites W2076254891 @default.
- W3122864963 cites W2076497939 @default.
- W3122864963 cites W2076515696 @default.
- W3122864963 cites W2077817323 @default.
- W3122864963 cites W2078884620 @default.
- W3122864963 cites W2079372760 @default.
- W3122864963 cites W2081016149 @default.