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Molecular Dynamics Simulation of the Interaction of Two Linear Battacin Analogs with Model Gram-Positive and Gram-Negative Bacterial Cell Membranes.

ABSTRACT: Antimicrobial peptides (AMPs) are a potential solution to the increasing threat of antibiotic resistance, but successful design of active but nontoxic AMPs requires understanding their mechanism of action. Molecular dynamics (MD) simulations can provide atomic-level information regarding how AMPs interact with the cell membrane. Here, we have used MD simulations to study two linear analogs of battacin, a naturally occurring cyclic, lipidated, nonribosomal AMP. Like battacin, these analogs are active against Gram-negative multidrug resistant and Gram-positive bacteria, but they are less toxic than battacin. Our simulations show that this activity depends upon a combination of positively charged and hydrophobic moieties. Favorable interactions with negatively charged membrane lipid head groups drive association with the membrane and insertion of hydrophobic residues, and the N-terminal lipid anchors the peptides to the membrane surface. Both effects are required for stable membrane binding.

SUBMITTER: Chakraborty A

PROVIDER: S-EPMC7807746 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Molecular Dynamics Simulation of the Interaction of Two Linear Battacin Analogs with Model Gram-Positive and Gram-Negative Bacterial Cell Membranes.

Chakraborty Aparajita A Kobzev Elisey E Chan Jonathan J de Zoysa Gayan Heruka GH Sarojini Vijayalekshmi V Piggot Thomas J TJ Allison Jane R JR

ACS omega 20201222 1

Antimicrobial peptides (AMPs) are a potential solution to the increasing threat of antibiotic resistance, but successful design of active but nontoxic AMPs requires understanding their mechanism of action. Molecular dynamics (MD) simulations can provide atomic-level information regarding how AMPs interact with the cell membrane. Here, we have used MD simulations to study two linear analogs of battacin, a naturally occurring cyclic, lipidated, nonribosomal AMP. Like battacin, these analogs are ac ...[more]

PMID: 33458490

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Dataset Information

Molecular Dynamics Simulation of the Interaction of Two Linear Battacin Analogs with Model Gram-Positive and Gram-Negative Bacterial Cell Membranes.

Publications

Molecular Dynamics Simulation of the Interaction of Two Linear Battacin Analogs with Model Gram-Positive and Gram-Negative Bacterial Cell Membranes.

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