Surface binding of alamethicin stabilizes its helical structure: molecular dynamics simulations.
Alamethicin is an amphipathic alpha-helical peptide that forms ion channels. An early event in channel formation is believed to be the binding of alamethicin to the surface of a lipid bilayer. Molecular dynamics simulations are used to compare the structural and dynamic properties of alamethicin in water and alamethicin bound to the surface of a phosphatidylcholine bilayer. The bilayer surface simulation corresponded to a loosely bound alamethicin molecule that interacted with lipid headgroups but did not penetrate the hydrophobic core of the bilayer. Both simulations started with the peptide molecule in an alpha-helical conformation and lasted 2 ns. In water, the helix started to unfold after approximately 300 ps and by the end of the simulation only the N-terminal region of the peptide remained alpha-helical and the molecule had collapsed into a more compact form. At the surface of the bilayer, loss of helicity was restricted to the C-terminal third of the molecule and the rod-shaped structure of the peptide was retained. In the surface simulation about 10% of the peptide/water H-bonds were replaced by peptide/lipid H-bonds. These simulations suggest that some degree of stabilization of an amphipathic alpha-helix occurs at a bilayer surface even without interactions between hydrophobic side chains and the acyl chain core of the bilayer.
Tieleman
D P
DP
BIOSON Research Institute and Department of Biophysical Chemistry, University of Groningen, Groningen, The Netherlands.
Berendsen
H J
HJ
Sansom
M S
MS
D000408:Alamethicin / Q000737:chemistry*; D055592:Biophysical Phenomena; D001703:Biophysics; D007473:Ion Channels / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry; D008958:Models, Molecular; D010713:Phosphatidylcholines / Q000737:chemistry; D017433:Protein Structure, Secondary; D013816:Thermodynamics; D014867:Water
D007473:Ion Channels; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D014867:Water; D000408:Alamethicin