Article: Molecular dynamics simulation of the interactions of antimicrobial peptides with phospholipids of the inner membrane of gram-negative bacteria Journal: International Journal of Computational Biology and Drug Design (IJCBDD) 2024 Vol.16 No.1 pp.42 - 55 Abstract: Antimicrobial peptides (AMP), positively charged polypeptides, are now extensively studied in the world to develop efficient drugs against extremely resistant bacterial strains. By molecular dynamics (MD) simulations, there were studied the ligand-receptor interactions of polymyxin B with two model systems in the water-salt solution: an anionic sodium dodecyl sulphate (SDS) micelle and explicit lipid bilayer of zwitterionic phosphatidylethanolamine (PEA), which mimics the gram-negative bacteria membrane. As a result, the polymyxin binding to PEA is stronger. The polymyxin B molecule interacts differently with these two types of membrane mimetics. The interaction of the peptide with SDS micelle occurs mainly due to electrostatic interactions and/or hydrogen bonding interactions of protonated Dab groups and polar groups of polymyxin with charged and polar groups of SDS micelles. The interaction of the peptide with the DPC micelle occurs mainly by the hydrophobic interactions of its Phe, Leu, and methyloctanoyl. Inderscience Publishers - linking academia, business and industry through research

Title: Molecular dynamics simulation of the interactions of antimicrobial peptides with phospholipids of the inner membrane of gram-negative bacteria

Authors: Yury Lisnyak; Artur Martynov; Boris Farber

Addresses: Deceased, formerly of: I. Mechnikov Institute of Microbiology and Immunology, National Academy of Medical Sciences of Ukraine, 14/16, Pushkinska Str., Kharkiv, 61057, Ukraine ' I. Mechnikov Institute of Microbiology and Immunology, National Academy of Medical Sciences of Ukraine, 14/16, Pushkinska Str., Kharkiv, 61057, Ukraine ' Noigel LLC, 225 Broadway, Suite 1420, New York City, 10007, USA

Abstract: Antimicrobial peptides (AMP), positively charged polypeptides, are now extensively studied in the world to develop efficient drugs against extremely resistant bacterial strains. By molecular dynamics (MD) simulations, there were studied the ligand-receptor interactions of polymyxin B with two model systems in the water-salt solution: an anionic sodium dodecyl sulphate (SDS) micelle and explicit lipid bilayer of zwitterionic phosphatidylethanolamine (PEA), which mimics the gram-negative bacteria membrane. As a result, the polymyxin binding to PEA is stronger. The polymyxin B molecule interacts differently with these two types of membrane mimetics. The interaction of the peptide with SDS micelle occurs mainly due to electrostatic interactions and/or hydrogen bonding interactions of protonated Dab groups and polar groups of polymyxin with charged and polar groups of SDS micelles. The interaction of the peptide with the DPC micelle occurs mainly by the hydrophobic interactions of its Phe, Leu, and methyloctanoyl.

Keywords: drug-target interactions; molecular dynamics simulations; polymyxin B; micelles; antimicrobial peptides; polymyxin; lipopolysaccharide.

DOI: 10.1504/IJCBDD.2024.139487

International Journal of Computational Biology and Drug Design, 2024 Vol.16 No.1, pp.42 - 55

Received: 14 Oct 2022
Accepted: 21 Nov 2023
Published online: 02 Jul 2024 *

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Title: Molecular dynamics simulation of the interactions of antimicrobial peptides with phospholipids of the inner membrane of gram-negative bacteria

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