title: Combined use of replica-exchange molecular dynamics and magic-angle-spinning solid-state NMR spectral simulations for determining the structure and orientation of membrane-bound peptide.
abstract: We report an approach to determining membrane peptides and membrane protein complex structures by magic-angle-spinning solid-state NMR and molecular dynamics simulation. First, an ensemble of low energy structures of mastoparan-X, a wasp venom peptide, in lipid bilayers was generated by replica exchange molecular dynamics (REMD) simulation with the implicit membrane/solvent model. Next, peptide structures compatible with experimental (13)C(α), C(β), and C' chemical shifts were selected from the ensemble. The (13)C(α) chemical shifts alone were sufficient for the selection with backbone rmsd's of ∼0.8 Å from the experimentally determined structure. The dipolar couplings between the peptide protons and lipid (2)H/(31)P nuclei were obtained from the (13)C-observed (2)H/(31)P-selective (1)H-demagnetization experiments for selecting the backbone and side chain structures relative to the membrane. The simulated structure agreed with the experimental one in the depth and orientation. The REMD simulation can be used for supplementing the limited structural constraints obtainable from the solid-state NMR spectra.
authors.affiliation: Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita 565-0871 Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ikeda
authors.forename: Tomoshi
authors.initials: T
authors.lastname: Kameda
authors.forename: Erisa
authors.initials: E
authors.lastname: Harada
authors.forename: Hideo
authors.initials: H
authors.lastname: Akutsu
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Fujiwara
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D008051:Lipid Bilayers / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D014862:Wasp Venoms
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D008051:Lipid Bilayers; D010455:Peptides; D010743:Phospholipids; D014862:Wasp Venoms; C071123:mastoparan X