title: Computer simulation of the distribution of hexane in a lipid bilayer: spatially resolved free energy, entropy, and enthalpy profiles.
abstract: The partitioning behavior of small molecules in lipid bilayers is important in a variety of areas including membrane protein folding and pharmacology. However, the inhomogeneous nature of lipid bilayers on a nanometer length scale complicates experimental studies of membrane partitioning. To gain more insight in the partitioning of a small molecule into the lipid bilayer, we have carried out atomistic computer simulations of hexane in a dioleoyl phosphatidylcholine model membrane. We have been able to obtain spatially resolved free energy, entropy, enthalpy, and heat capacity profiles based on umbrella sampling calculations at three different temperatures. In agreement with experiment, hexane partitions preferentially to the center of the bilayer. This process is driven almost entirely by a favorable entropy change, consistent with the hydrophobic effect. In contrast, partitioning to the densest region of the acyl chains is dominated by a favorable enthalpy change with a small entropy change, which is consistent with the "nonclassical" hydrophobic effect or "bilayer" effect. We explain the features of the entropy and enthalpy profiles in terms of density and free volume in the system.
authors.affiliation: Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta T2N 1N4, Canada.
authors.forename: Justin L
authors.initials: JL
authors.lastname: MacCallum
authors.forename: D Peter
authors.initials: DP
authors.lastname: Tieleman
mesh_terms: D003198:Computer Simulation; D019277:Entropy; D006586:Hexanes / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry*; D008956:Models, Chemical; D010713:Phosphatidylcholines / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D006586:Hexanes; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; C017251:1,2-oleoylphosphatidylcholine