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Biophys J. 2006 Mar 15;90(6):1855-64. Epub 2005 Dec 30.

Conformation and environment of channel-forming peptides: a simulation study.

Author information

1
Department of Biochemistry, University of Oxford, Oxford, United Kingdom OX1 3QU.

Abstract

Ion channel-forming peptides enable us to study the conformational dynamics of a transmembrane helix as a function of sequence and environment. Molecular dynamics simulations are used to study the conformation and dynamics of three 22-residue peptides derived from the second transmembrane domain of the glycine receptor (NK4-M2GlyR-p22). Simulations are performed on the peptide in four different environments: trifluoroethanol/water; SDS micelles; DPC micelles; and a DMPC bilayer. A hierarchy of alpha-helix stabilization between the different environments is observed such that TFE/water < micelles < bilayers. Local clustering of trifluoroethanol molecules around the peptide appears to help stabilize an alpha-helical conformation. Single (S22W) and double (S22W,T19R) substitutions at the C-terminus of NK4-M2GlyR-p22 help to stabilize a helical conformation in the micelle and bilayer environments. This correlates with the ability of the W22 and R19 side chains to form H-bonds with the headgroups of lipid or detergent molecules. This study provides a first atomic resolution comparison of the structure and dynamics of NK4-M2GlyR-p22 peptides in membrane and membrane-mimetic environments, paralleling NMR and functional studies of these peptides.

PMID:
16387778
PMCID:
PMC1386767
DOI:
10.1529/biophysj.105.069625
[Indexed for MEDLINE]
Free PMC Article

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