title: Predicting solute partitioning in lipid bilayers: Free energies and partition coefficients from molecular dynamics simulations and COSMOmic.
abstract: Quantitative predictions of biomembrane/water partition coefficients are important, as they are a key property in pharmaceutical applications and toxicological studies. Molecular dynamics (MD) simulations are used to calculate free energy profiles for different solutes in lipid bilayers. How to calculate partition coefficients from these profiles is discussed in detail and different definitions of partition coefficients are compared. Importantly, it is shown that the calculated coefficients are in quantitative agreement with experimental results. Furthermore, we compare free energy profiles from MD simulations to profiles obtained by the recent method COSMOmic, which is an extension of the conductor-like screening model for realistic solvation to micelles and biomembranes. The free energy profiles from these molecular methods are in good agreement. Additionally, solute orientations calculated with MD and COSMOmic are compared and again a good agreement is found. Four different solutes are investigated in detail: 4-ethylphenol, propanol, 5-phenylvaleric acid, and dibenz[a,h]anthracene, whereby the latter belongs to the class of polycyclic aromatic hydrocarbons. The convergence of the free energy profiles from biased MD simulations is discussed and the results are shown to be comparable to equilibrium MD simulations. For 5-phenylvaleric acid the influence of the carboxyl group dihedral angle on free energy profiles is analyzed with MD simulations.
authors.affiliation: Institute of Thermal Separation Processes, Hamburg University of Technology, Eissendorfer Str. 38, 21073 Hamburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Jakobtorweihen
authors.affiliation: Institute of Chemical Reaction Engineering, Hamburg University of Technology, Eissendorfer Str. 38, 21073 Hamburg, Germany.
authors.forename: A Chaides
authors.initials: AC
authors.lastname: Zuniga
authors.affiliation: Institute of Thermal Separation Processes, Hamburg University of Technology, Eissendorfer Str. 38, 21073 Hamburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Ingram
authors.affiliation: Institute of Thermal Separation Processes, Hamburg University of Technology, Eissendorfer Str. 38, 21073 Hamburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Gerlach
authors.affiliation: Institute of Chemical Reaction Engineering, Hamburg University of Technology, Eissendorfer Str. 38, 21073 Hamburg, Germany.
authors.forename: F J
authors.initials: FJ
authors.lastname: Keil
authors.affiliation: Institute of Thermal Separation Processes, Hamburg University of Technology, Eissendorfer Str. 38, 21073 Hamburg, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Smirnova
mesh_terms: D000433:1-Propanol / Q000737:chemistry*; D001551:Benz(a)Anthracenes / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry*; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D010421:Pentanoic Acids / Q000737:chemistry*; D010636:Phenols / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D001551:Benz(a)Anthracenes; D008051:Lipid Bilayers; D010421:Pentanoic Acids; D010636:Phenols; C016365:dibenzanthracenes; D000433:1-Propanol; C042291:4-ethylphenol; C400347:5-phenylvaleric acid