title: Alamethicin helices in a bilayer and in solution: molecular dynamics simulations.
abstract: Alamethicin is an alpha-helical channel-forming peptide, which inserts into lipid bilayers in a voltage-dependent, asymmetrical fashion. Nanosecond molecular dynamics simulations have been used to compare alamethicin conformation and dynamics in three different environments: 1) in water; 2) in methanol; and 3) inserted into a lipid (palmitoyl-oleoyl-phosphatidylcholine) bilayer to form a transmembrane helix. In the bilayer and in methanol, there was little change (Calpha RMSD approximately 0.2 nm over 2 ns and 1 ns) from the initial helical conformation of the peptide. In water there were substantial changes (Calpha RMSD approximately 0.4 nm over 1 ns), especially in the C-terminal segment of the peptide, which lost its alpha-helical conformation. In the bilayer and in methanol, the alamethicin molecule underwent hinge-bending motion about its central Gly-X-X-Pro sequence motif. Analysis of H-bonding interactions revealed that the polar C-terminal side chains of alamethicin provided an "anchor" to the bilayer/water interface via formation of multiple H-bonds that persisted throughout the simulation. This explains why the preferred mode of helix insertion into the bilayer is N-terminal, which is believed to underlie the asymmetry of voltage activation of alamethicin channels.
authors.affiliation: BIOSON Research Institute and Department of Biophysical Chemistry, University of Groningen, 9747 AG Groningen, The Netherlands.
authors.forename: D P
authors.initials: DP
authors.lastname: Tieleman
authors.forename: M S
authors.initials: MS
authors.lastname: Sansom
authors.forename: H J
authors.initials: HJ
authors.lastname: Berendsen
mesh_terms: D000408:Alamethicin / Q000737:chemistry*; D000595:Amino Acid Sequence; D055592:Biophysical Phenomena; D001703:Biophysics; D003198:Computer Simulation; D008051:Lipid Bilayers / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010713:Phosphatidylcholines / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012996:Solutions; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D012996:Solutions; D000408:Alamethicin; C028694:1-palmitoyl-2-oleoylphosphatidylcholine