Molecular Simulations of Melittin-Induced Membrane Pores
(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.
(Less)
- author
- Sun, Delin ; Forsman, Jan LU and Woodward, Clifford E.
- organization
- publishing date
- 2017-11-09
- 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 (ACS)
- external identifiers
-
- pmid:29035531
- wos:000415140000003
- scopus:85033565300
- 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
- 2024-03-31 18:58:17
@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 (ACS)}},
series = {{Journal of Physical Chemistry B}},
title = {{Molecular Simulations of Melittin-Induced Membrane Pores}},
url = {{http://dx.doi.org/10.1021/acs.jpcb.7b07126}},
doi = {{10.1021/acs.jpcb.7b07126}},
volume = {{121}},
year = {{2017}},
}