Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pcbi.1004180
Title: Interaction of the Antimicrobial Peptide Polymyxin B1 with Both Membranes of E. coli: A Molecular Dynamics Study
Authors: Berglund N.A.
Piggot T.J.
Jefferies D.
Sessions R.B.
Bond P.J. 
Khalid S.
Keywords: lipid A
lipopolysaccharide
polymyxin derivative
polymyxin
polymyxin B(1)
antimicrobial activity
Article
bacterial membrane
Escherichia coli
hydration
inner membrane
membrane stabilization
molecular dynamics
nonhuman
outer membrane
protein aggregation
protein interaction
analogs and derivatives
biology
cell membrane
chemistry
Escherichia coli
metabolism
molecular dynamics
Bacteria (microorganisms)
Negibacteria
Cell Membrane
Computational Biology
Escherichia coli
Lipopolysaccharides
Molecular Dynamics Simulation
Polymyxins
Issue Date: 2015
Citation: Berglund N.A., Piggot T.J., Jefferies D., Sessions R.B., Bond P.J., Khalid S. (2015). Interaction of the Antimicrobial Peptide Polymyxin B1 with Both Membranes of E. coli: A Molecular Dynamics Study. PLoS Computational Biology 11 (4) : e1004180. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pcbi.1004180
Rights: Attribution 4.0 International
Abstract: Antimicrobial peptides are small, cationic proteins that can induce lysis of bacterial cells through interaction with their membranes. Different mechanisms for cell lysis have been proposed, but these models tend to neglect the role of the chemical composition of the membrane, which differs between bacterial species and can be heterogeneous even within a single cell. Moreover, the cell envelope of Gram-negative bacteria such as E. coli contains two membranes with differing compositions. To this end, we report the first molecular dynamics simulation study of the interaction of the antimicrobial peptide, polymyxin B1 with complex models of both the inner and outer membranes of E. coli. The results of >16 microseconds of simulation predict that polymyxin B1 is likely to interact with the membranes via distinct mechanisms. The lipopeptides aggregate in the lipopolysaccharide headgroup region of the outer membrane with limited tendency for insertion within the lipid A tails. In contrast, the lipopeptides readily insert into the inner membrane core, and the concomitant increased hydration may be responsible for bilayer destabilization and antimicrobial function. Given the urgent need to develop novel, potent antibiotics, the results presented here reveal key mechanistic details that may be exploited for future rational drug development. ? 2015 Berglund et al.
Source Title: PLoS Computational Biology
URI: https://scholarbank.nus.edu.sg/handle/10635/161937
ISSN: 1553734X
DOI: 10.1371/journal.pcbi.1004180
Rights: Attribution 4.0 International
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