BIROn - Birkbeck Institutional Research Online

    Reorientation and dimerization of the membrane-bound antimicrobial Peptide PGLa from microsecond all-atom MD simulations

    Ulmschneider, J.P. and Smith, J.C. and Ulmschneider, Martin B. and Ulrich, A.S. and Strandberg, E. (2012) Reorientation and dimerization of the membrane-bound antimicrobial Peptide PGLa from microsecond all-atom MD simulations. Biophysical Journal 103 (3), pp. 472-482. ISSN 0006-3495.

    Full text not available from this repository.

    Abstract

    The membrane-active antimicrobial peptide PGLa from Xenopus laevis is known from solid-state 2H-, 15N-, and 19F-NMR spectroscopy to occupy two distinct α-helical surface adsorbed states in membranes: a surface-bound S-state with a tilt angle of ∼95° at low peptide/lipid molar ratio (P/L = 1:200), and an obliquely tilted T-state with a tilt angle of 127° at higher peptide concentration (P/L = 1:50). Using a rapid molecular-dynamics insertion protocol in combination with microsecond-scale simulation, we have characterized the structure of both states in detail. As expected, the amphiphilic peptide resides horizontally on the membrane surface in a monomeric form at a low P/L, whereas the T-state is seen in the simulations to be a symmetric antiparallel dimer, with close contacts between small glycine and alanine residues at the interface. The computed tilt angles and azimuthal rotations, as well as the quadrupolar splittings predicted from the simulations agree with the experimental NMR data. The simulations reveal many structural details previously inaccessible, such as the immersion depth of the peptide in the membrane and the packing of the dimerization interface. The study highlights the ability and limitations of current state-of-the-art multimicrosecond all-atom simulations of membrane-active peptides to complement experimental data from solid-state NMR.

    Metadata

    Item Type: Article
    School: Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences
    Depositing User: Administrator
    Date Deposited: 10 Sep 2012 11:22
    Last Modified: 02 Aug 2023 16:58
    URI: https://eprints.bbk.ac.uk/id/eprint/5067

    Statistics

    Activity Overview
    6 month trend
    0Downloads
    6 month trend
    239Hits

    Additional statistics are available via IRStats2.

    Archive Staff Only (login required)

    Edit/View Item Edit/View Item