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Molecular dynamics simulations of cholesterol-rich membranes using a coarse-grained force field for cyclic alkanes

Journal Article · · Journal of Chemical Physics
DOI:https://doi.org/10.1063/1.4937153· OSTI ID:22493383
;  [1];  [2];  [3];  [4];  [5]
  1. Institute for Computational Molecular Science, Temple University, 1925 North 12th Street, Philadelphia, Pennsylvania 19122-1801 (United States)
  2. Department of Chemistry, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016 (India)
  3. Modeling and Simulation, Corporate Research and Development, The Procter and Gamble Company, West Chester, Ohio 45069 (United States)
  4. Department of Applied Chemistry, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 (Japan)
  5. Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland 20742 (United States)

The architecture of a biological membrane hinges upon the fundamental fact that its properties are determined by more than the sum of its individual components. Studies on model membranes have shown the need to characterize in molecular detail how properties such as thickness, fluidity, and macroscopic bending rigidity are regulated by the interactions between individual molecules in a non-trivial fashion. Simulation-based approaches are invaluable to this purpose but are typically limited to short sampling times and model systems that are often smaller than the required properties. To alleviate both limitations, the use of coarse-grained (CG) models is nowadays an established computational strategy. We here present a new CG force field for cholesterol, which was developed by using measured properties of small molecules, and can be used in combination with our previously developed force field for phospholipids. The new model performs with precision comparable to atomistic force fields in predicting the properties of cholesterol-rich phospholipid bilayers, including area per lipid, bilayer thickness, tail order parameter, increase in bending rigidity, and propensity to form liquid-ordered domains in ternary mixtures. We suggest the use of this model to quantify the impact of cholesterol on macroscopic properties and on microscopic phenomena involving localization and trafficking of lipids and proteins on cellular membranes.

OSTI ID:
22493383
Journal Information:
Journal of Chemical Physics, Journal Name: Journal of Chemical Physics Journal Issue: 24 Vol. 143; ISSN JCPSA6; ISSN 0021-9606
Country of Publication:
United States
Language:
English

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A coarse-grain model for entangled polyethylene melts and polyethylene crystallization journal June 2019
Direct Derivation of Free Energies of Membrane Deformation and Other Solvent Density Variations From Enhanced Sampling Molecular Dynamics journal October 2019
DMSO induced dehydration of heterogeneous lipid bilayers and its impact on their structures journal December 2019
Lipid Droplet Biogenesis is Driven by Liquid-Liquid Phase Separation journal January 2020
Cholesterol provides nonsacrificial protection of membrane lipids from chemical damage at air–water interface journal March 2018
Local accumulation of diacylglycerol alters membrane properties nonlinearly due to its transbilayer activity journal June 2019
The asymmetry of plasma membranes and their cholesterol content influence the uptake of cisplatin journal April 2019
Coexistence of lipid phases stabilizes interstitial water in the outer layer of mammalian skin posted_content October 2019
Lipid droplet biogenesis is driven by liquid-liquid phase separation posted_content January 2020
Cholesterol in phospholipid bilayers: positions and orientations inside membranes with different unsaturation degrees journal January 2019

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