title: All-atom simulations and free-energy calculations of coiled-coil peptides with lipid bilayers: binding strength, structural transition, and effect on lipid dynamics.
abstract: Peptides E and K, which are synthetic coiled-coil peptides for membrane fusion, were simulated with lipid bilayers composed of lipids and cholesterols at different ratios using all-atom models. We first calculated free energies of binding from umbrella sampling simulations, showing that both E and K peptides tend to adsorb onto the bilayer surface, which occurs more strongly in the bilayer composed of smaller lipid headgroups. Then, unrestrained simulations show that K peptides more deeply insert into the bilayer with partially retaining the helical structure, while E peptides less insert and predominantly become random coils, indicating the structural transition from helices to random coils, in quantitative agreement with experiments. This is because K peptides electrostatically interact with lipid phosphates, as well as because hydrocarbons of lysines of K peptide are longer than those of glutamic acids of E peptide and thus form stronger hydrophobic interactions with lipid tails. This deeper insertion of K peptide increases the bilayer dynamics and a vacancy below the peptide, leading to the rearrangement of smaller lipids. These findings help explain the experimentally observed or proposed differences in the insertion depth, binding strength, and structural transition of E and K peptides, and support the snorkeling effect.
authors.affiliation: Department of Chemical Engineering, Dankook University, Yongin, 448-701, South Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Woo
authors.affiliation: Department of Chemical Engineering, Dankook University, Yongin, 448-701, South Korea.
authors.forename: Hwankyu
authors.initials: H
authors.lastname: Lee
mesh_terms: D002784:Cholesterol / Q000737:chemistry; D003198:Computer Simulation; D004745:Enkephalins / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D008561:Membrane Fusion; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D055672:Static Electricity; D023083:beta-Defensins / Q000737:chemistry*
chemical_list: D004745:Enkephalins; C551850:FSPQMLQDIIEKKTKIL; D008051:Lipid Bilayers; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D023083:beta-Defensins; C094877:dioleoyl phosphatidylethanolamine; C039933:peptide E (adrenal medulla); D002784:Cholesterol; C017251:1,2-oleoylphosphatidylcholine