Open AccessMolecular Dynamics Simulation of the Interaction of Two Linear Battacin Analogs with Model Gram-Positive and Gram-Negative Bacterial Cell Membranes
Author(s) -
Aruna Chakraborty,
Elisey Kobzev,
Jimmy W.M. Chan,
Gayan Heruka De Zoysa,
Vijayalekshmi Sarojini,
Thomas J. Piggot,
Jane R. Allison
Publication year - 2020
Publication title -
acs omega
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.779
H-Index - 40
ISSN - 2470-1343
DOI - 10.1021/acsomega.0c04752
Subject(s) - membrane , molecular dynamics , antimicrobial peptides , biophysics , gram negative bacteria , cell membrane , chemistry , gram , hydrophobic effect , dynamics (music) , multiple drug resistance , peptide , bacteria , combinatorial chemistry , biochemistry , biology , antibiotics , computational chemistry , escherichia coli , physics , genetics , gene , acoustics
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.