Wang, Yi; Schlamadinger, Diana E.; Kim, Judy E.; McCammon, J. Andrew
Comparative molecular dynamics simulations of the antimicrobial peptide CM15 in model lipid bilayers
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1818:1402-1409, MAY 2012

We report altogether 3-mu s molecular dynamics (MD) simulations of the antimicrobial peptide CM15 to systematically investigate its interaction with two model lipid bilayers, pure POPC and mixed POPG:POPC (1:2). Starting with either an alpha-helical or a random-coil conformation, CM15 is found to insert into both bilayers. Peptide-lipid interaction is stronger with the anionic POPG:POPC than the zwitterionic POPC, which is largely attributed to the electrostatic attraction between CM15 and the negatively charged POPG. Simulations initiated with CM15 as a random coil allowed us to study peptide folding at the lipid-water interface. Interestingly, CM15 folding appears to be faster in POPC than POPG:POPC. which may be explained by a lower activation energy barrier of structural rearrangement in the former system. Our data also suggest that compared with the random-coil conformation, CM15 in a pre-folded alpha-helix has significantly reduced interactions with the lipids, indicating that peptide initial structures may bias the simulation results considerably on the 100-ns timescale. The implications of this result should be considered when preparing and interpreting future AMP simulations. (C) 2012 Elsevier B.V. All rights reserved.

DOI:10.1016/j.bbamem.2012.02.017

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