title: Effective energy function for proteins in lipid membranes.
abstract: A simple extension of the EEF1 energy function to heterogeneous membrane-aqueous media is proposed. The extension consists of (a) development of solvation parameters for a nonpolar phase using experimental data for the transfer of amino acid side-chains from water to cyclohexane, (b) introduction of a heterogeneous membrane-aqueous system by making the reference solvation free energy of each atom dependent on the vertical coordinate, (c) a modification of the distance-dependent dielectric model to account for reduced screening of electrostatic interactions in the membrane, and (d) an adjustment of the EEF1 aqueous model in light of recent calculations of the potential of mean force between amino acid side-chains in water. The electrostatic model is adjusted to match experimental observations for polyalanine, polyleucine, and the glycophorin A dimer. The resulting energy function (IMM1) reproduces the preference of Trp and Tyr for the membrane interface, gives reasonable energies of insertion into or adsorption onto a membrane, and allows stable 1-ns MD simulations of the glycophorin A dimer. We find that the lowest-energy orientation of melittin in bilayers varies, depending on the thickness of the hydrocarbon layer.
authors.affiliation: Department of Chemistry, City College of the City University of New York, New York 10031, USA. themis@sci.ccny.cuny.edu
authors.forename: Themis
authors.initials: T
authors.lastname: Lazaridis
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D001436:Bacteriorhodopsins / Q000737:chemistry; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D006021:Glycophorins / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D008555:Melitten / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012997:Solvents / Q000737:chemistry; D055672:Static Electricity; D014364:Tryptophan / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry
chemical_list: D000596:Amino Acids; D006021:Glycophorins; D008051:Lipid Bilayers; D008565:Membrane Proteins; D010455:Peptides; D012997:Solvents; C080383:peptide 18A; D008555:Melitten; C019529:polyalanine; C027819:polyleucine; D014443:Tyrosine; D001436:Bacteriorhodopsins; D014364:Tryptophan