Molecular Crowding Alters the Interactions of Polymyxin Lipopeptides within the Periplasm of E. coli: Insights from Molecular Dynamics

• DOI: 10.1021/acs.jpcb.3c07985
• Publication Date: 2024-03-08T18:40:27Z
• Authors: Iain P. S. Smith; Conrado Pedebos; Syma Khalid
• Keywords: Polymyxin; Cell envelope; Gram-Negative Bacteria; Polymyxin B

The cell envelope of Gram-negative bacteria is a crowded tripartite architecture that separates the interior from external environment. Two membranes encapsulate aqueous periplasm, which contains wall. Little known about mechanisms via antimicrobial peptides move through periplasm outer membrane to their site action, inner membrane. We utilize all-atom molecular dynamics study two peptides, polymyxins B1 and E, within models E. coli different extents. In simple chemical environment, both PMB1 PME bind irreversibly presence specific macromolecules leads competition with for wall interaction sites, resulting in polymyxin dissociation Chemical complexity also impacts interactions between Braun's lipoprotein; thus, modes lipoprotein antibiotics are dependent upon nature other species present.