title: Molecular dynamics simulations of cholesterol-rich membranes using a coarse-grained force field for cyclic alkanes.
abstract: 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.
authors.affiliation: Institute for Computational Molecular Science, Temple University, 1925 North 12th Street, Philadelphia, Pennsylvania 19122-1801, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: MacDermaid
authors.affiliation: Department of Chemistry, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India.
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Kashyap
authors.affiliation: Modeling and Simulation, Corporate Research and Development, The Procter and Gamble Company, West Chester, Ohio 45069, USA.
authors.forename: Russell H
authors.initials: RH
authors.lastname: DeVane
authors.affiliation: Department of Applied Chemistry, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Shinoda
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, Maryland 20742, USA.
authors.forename: Jeffery B
authors.initials: JB
authors.lastname: Klauda
authors.affiliation: Institute for Computational Molecular Science, Temple University, 1925 North 12th Street, Philadelphia, Pennsylvania 19122-1801, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Klein
authors.affiliation: Institute for Computational Molecular Science, Temple University, 1925 North 12th Street, Philadelphia, Pennsylvania 19122-1801, USA.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Fiorin
mesh_terms: D000473:Alkanes / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010743:Phospholipids / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000473:Alkanes; D008051:Lipid Bilayers; D010743:Phospholipids; D002784:Cholesterol