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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.

Original publication

DOI

10.1016/S0006-3495(99)77176-6

Type

Journal article

Journal

Biophys J

Publication Date

01/1999

Volume

76

Pages

40 - 49

Keywords

Alamethicin, Amino Acid Sequence, Biophysical Phenomena, Biophysics, Computer Simulation, Lipid Bilayers, Models, Molecular, Molecular Sequence Data, Phosphatidylcholines, Protein Conformation, Protein Structure, Secondary, Solutions, Thermodynamics