Conformation and environment of channel-forming peptides: a simulation study.
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.
Johnston
Jennifer M
JM
Department of Biochemistry, University of Oxford, Oxford, United Kingdom OX1 3QU.
Cook
Gabriel A
GA
Tomich
John M
JM
Sansom
Mark S P
MS
D003198:Computer Simulation; D015640:Ion Channel Gating; D008051:Lipid Bilayers / Q000737:chemistry*; D008560:Membrane Fluidity; D008956:Models, Chemical; D008958:Models, Molecular; D009038:Motion; D010455:Peptides / Q000737:chemistry*; D016062:Porosity; D011487:Protein Conformation; D018009:Receptors, Glycine / Q000737:chemistry*; D013329:Structure-Activity Relationship
D008051:Lipid Bilayers; D010455:Peptides; D018009:Receptors, Glycine