title: Coarse-grained molecular dynamics of tetrameric transmembrane peptide bundles within a lipid bilayer.
abstract: The conformations of model transmembrane peptides are studied to understand the structural and dynamical aspects of tetrameric bundles using a series of coarse grain (CG) molecular dynamics (MD) simulations since membrane proteins play a crucial role in cell function. In this work, two different amphipathic models have been constructed using similar hydrophobic/hydrophilic characteristics with two structurally distinct morphologies to evaluate the effect of roughness and hydrophilic topology on the structure of tetrameric bundles, one class that forms an ion-channel and one class that does not. Free energy calculations of typical amphipathic peptide topologies show that using a relatively smooth surface morphology allows for a stable conformation of the tetramer bundle in a diamond formation. However, the model with side chains attached to the core in order to roughen the surface has a stable square tetramer bundle which is consistent with experimental data and all-atom (AA) MD simulations. Comparisons of the CG simulations with AA MD simulations are in reasonable agreement with the formation of tetrameric homo-oligomers, partitioning within the lipid bilayer and tilt angle with respect to the bilayer normal. We concluded that a square or diamond shape tetrameric homo-oligomers could be stabilized by rational design of the peptide morphology and topology of the surface, thus allowing us to tune the permeability of the bundle or channel.
authors.affiliation: Department of Chemistry & Biochemistry and the West Center for Computational Chemistry and Drug Design, University of the Sciences in Philadelphia, 600 South 43rd Street, Philadelphia, PA 19104-4495, United States.
authors.forename: Thuy Hien T
authors.initials: TH
authors.lastname: Nguyen
authors.forename: Niny Z
authors.initials: NZ
authors.lastname: Rao
authors.forename: William M
authors.initials: WM
authors.lastname: Schroeder
authors.forename: Preston B
authors.initials: PB
authors.lastname: Moore
mesh_terms: D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins; D010455:Peptides; D004134:Dimyristoylphosphatidylcholine