Simulations of octapeptin-outer membrane interactions reveal conformational flexibility is linked to antimicrobial potency.

ABSTRACT: The octapeptins are lipopeptide antibiotics that are structurally similar to polymyxins yet retain activity against polymyxin-resistant Gram-negative pathogens, suggesting they might be used to treat recalcitrant infections. However, the basis of their unique activity is unclear because of the difficulty in generating high-resolution experimental data of the interaction of antimicrobial peptides with lipid membranes. To elucidate these structure-activity relationships, we employed all-atom molecular dynamics simulations with umbrella sampling to investigate the conformational and energetic landscape of octapeptins interacting with bacterial outer membrane (OM). Specifically, we examined the interaction of octapeptin C4 and FADDI-115, lacking a single hydroxyl group compared with octapeptin

SUBMITTER: Jiang X 

PROVIDER: S-EPMC7681018 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature