Simulating the Mechanism of Antimicrobial Lipopeptides with All-Atom Molecular Dynamics

The emergence of antibiotic resistant pathogens is one of the major medical concerns of the 21st century, prompting renewed interest in the development of novel antimicrobial compounds. Here we use microsecond-scale all-atom molecular dynamics simulations to characterize the structure, dynamics, and...

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Bibliographic Details
Published in:Biochemistry (Easton) 2013-08, Vol.52 (33), p.5604-5610
Main Authors: Horn, Joshua N, Romo, Tod D, Grossfield, Alan
Format: Article
Language:English
Subjects:
Algorithms
Anti-Infective Agents - chemistry
Anti-Infective Agents - metabolism
Lipid Bilayers - chemistry
Lipid Bilayers - metabolism
Lipopeptides - chemistry
Lipopeptides - metabolism
Membrane Lipids - chemistry
Membrane Lipids - metabolism
Models, Molecular
Molecular Dynamics Simulation
Phosphatidylethanolamines - chemistry
Phosphatidylethanolamines - metabolism
Phosphatidylglycerols - chemistry
Phosphatidylglycerols - metabolism
Protein Binding
Time Factors
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Summary:The emergence of antibiotic resistant pathogens is one of the major medical concerns of the 21st century, prompting renewed interest in the development of novel antimicrobial compounds. Here we use microsecond-scale all-atom molecular dynamics simulations to characterize the structure, dynamics, and membrane-binding mechanism of a synthetic antimicrobial lipopeptide, C16-KGGK. Our simulations suggest that these lipopeptides prefer to aggregate in solution and alter the intrinsic order of the lipid bilayer upon binding. From these results and previous coarse-grained simulations, we have developed a simple model for the binding and insertion process for these lipopeptides.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi400773q