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Molecular Simulations of Melittin-Induced Membrane Pores

Sun, Delin; Forsman, Jan LU and Woodward, Clifford E. (2017) In Journal of Physical Chemistry B 121(44). p.10209-10214
Abstract

Membrane-active peptides (MAPs) are able to induce pores in cell membranes via molecular mechanisms, which are still subject to ongoing research. In this work, we present molecular dynamics simulations that suggest a precursor membrane defect plays an important role in the pore-inducing activity of the prototypical antimicrobial peptide melittin. The simulations reveal that the hydrophobic N-terminus of melittin is able to recognize and insert into the membrane defect in the lipid bilayer and that this leads to a cascading transfer of adsorbed peptides to the membrane defect, leading to peptide aggregation in the pore. We show that this mechanism also acts in the case of a melittin mutant without the flexible central proline hinge, thus... (More)

Membrane-active peptides (MAPs) are able to induce pores in cell membranes via molecular mechanisms, which are still subject to ongoing research. In this work, we present molecular dynamics simulations that suggest a precursor membrane defect plays an important role in the pore-inducing activity of the prototypical antimicrobial peptide melittin. The simulations reveal that the hydrophobic N-terminus of melittin is able to recognize and insert into the membrane defect in the lipid bilayer and that this leads to a cascading transfer of adsorbed peptides to the membrane defect, leading to peptide aggregation in the pore. We show that this mechanism also acts in the case of a melittin mutant without the flexible central proline hinge, thus indicating the latter is not crucial to the activity of melittin, which is consistent with experiments.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Physical Chemistry B
volume
121
issue
44
pages
6 pages
publisher
The American Chemical Society
external identifiers
  • scopus:85033565300
  • wos:000415140000003
ISSN
1520-6106
DOI
10.1021/acs.jpcb.7b07126
language
English
LU publication?
yes
id
eee80d07-f361-411f-adaa-a47f1a58b6c5
date added to LUP
2017-11-20 10:30:25
date last changed
2018-01-16 13:25:54
@article{eee80d07-f361-411f-adaa-a47f1a58b6c5,
  abstract     = {<p>Membrane-active peptides (MAPs) are able to induce pores in cell membranes via molecular mechanisms, which are still subject to ongoing research. In this work, we present molecular dynamics simulations that suggest a precursor membrane defect plays an important role in the pore-inducing activity of the prototypical antimicrobial peptide melittin. The simulations reveal that the hydrophobic N-terminus of melittin is able to recognize and insert into the membrane defect in the lipid bilayer and that this leads to a cascading transfer of adsorbed peptides to the membrane defect, leading to peptide aggregation in the pore. We show that this mechanism also acts in the case of a melittin mutant without the flexible central proline hinge, thus indicating the latter is not crucial to the activity of melittin, which is consistent with experiments.</p>},
  author       = {Sun, Delin and Forsman, Jan and Woodward, Clifford E.},
  issn         = {1520-6106},
  language     = {eng},
  month        = {11},
  number       = {44},
  pages        = {10209--10214},
  publisher    = {The American Chemical Society},
  series       = {Journal of Physical Chemistry B},
  title        = {Molecular Simulations of Melittin-Induced Membrane Pores},
  url          = {http://dx.doi.org/10.1021/acs.jpcb.7b07126},
  volume       = {121},
  year         = {2017},
}