title: Exploring peptide-membrane interactions with coarse-grained MD simulations.
abstract: The interaction of α-helical peptides with lipid bilayers is central to our understanding of the physicochemical principles of biological membrane organization and stability. Mutations that alter the position or orientation of an α-helix within a membrane, or that change the probability that the α-helix will insert into the membrane, can alter a range of membrane protein functions. We describe a comparative coarse-grained molecular dynamics simulation methodology, based on self-assembly of a lipid bilayer in the presence of an α-helical peptide, which allows us to model membrane transmembrane helix insertion. We validate this methodology against available experimental data for synthetic model peptides (WALP23 and LS3). Simulation-based estimates of apparent free energies of insertion into a bilayer of cystic fibrosis transmembrane regulator-derived helices correlate well with published data for translocon-mediated insertion. Comparison of values of the apparent free energy of insertion from self-assembly simulations with those from coarse-grained molecular dynamics potentials of mean force for model peptides, and with translocon-mediated insertion of cystic fibrosis transmembrane regulator-derived peptides suggests a nonequilibrium model of helix insertion into bilayers.
authors.affiliation: Oxford Centre for Integrative Systems Biology, University of Oxford, Oxford, United Kingdom.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Hall
authors.forename: Alan P
authors.initials: AP
authors.lastname: Chetwynd
authors.forename: Mark S P
authors.initials: MS
authors.lastname: Sansom
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000737:chemistry / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D015203:Reproducibility of Results; D013816:Thermodynamics; D013997:Time Factors
chemical_list: D008051:Lipid Bilayers; D010455:Peptides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator