MD simulations reveal how synthetic antimicrobial peptides interact with membrane models

Abstract

Since the discovery of antibiotics the extensive use in health care and agriculture has led to the development of resistant bacterial strains. Antimicrobial peptides (AMPs) exists in nature where they are believed to play an important role in the innate immune system in vertebrates. Due to their antibacterial properties and apparent ability to elicit very low bacterial resistance, researchers have been hopeful that they can alleviate the challenges of progressing multiresistance, but this has not become a reality yet.

In this project, molecular dynamics simulations are used to explore the interactions of AMPs with model lipid bilayers. An important step in this process is to obtain a lipid bilayer with structure and properties that resembles those of the biological relevant fluid phase (La) bilayer. By applying molecular dynamics it is possible to study the interaction at an atomic level. Atomic level studies of fluid phase (La) lipid bilayers are not possible with the present experimental methods.

To examine the atomic level interactions of the synthetic antimicrobial peptides RWR-NHBn and RTbtR-NHBn with a bacterial like membrane, various DMPC and DMPG lipid bilayers are simulated with different combinations of the ions Na+, K+ and Cl-. Most combination of ions yield membrane properties in good agreement with experimental values. A binary mixture of DMPC/DMPG with K+ as counter-ions is used for the simulation with peptides. Interesting effects on the membrane is seen in a system with 4 TRTbtR-NHBn peptides where one peptide cause a large groove in the membrane surface by suppressing many DMPG lipids in the region. This may be a pre-stage to pore formation.