Melittin, isolated from the venom of honeybee, is a representative antimicrobial peptide that cooperatively induces membrane pore formation. Antimicrobial actions caused by melittin have been investigated for the last three decades with both experiment and simulation. Understanding the melittin actions on the lipid bilayer is important to obtain insight into development of effective antimicrobial agents that form pores and directly kill bacteria. However, the detail of the melittin actions still has not been clearly elucidated due to the complexity of the actions and biological systems.<br/>To investigate the melittin actions on the lipid membrane, we performed a series of coarse-grained (CG) molecular dynamics (MD) simulations using the pSPICA force field (FF). The pSPICA FF was a CG force field based on the same philosophy as in the SPICA FF and designed with a polar CG water model. It reproduces several thermodynamics properties and is able to capture a melittin pore formation state similar to that observed in atomistic MD simulations and experiment.<br/>We built POPC lipid bilayer systems where melittin peptides were adsorbed on one side of the bilayer surface at a certain peptide/lipid (P/L) ratio and conducted 5 μs CG-MD simulations. For the system at P/L ≒ 1/50, we found a membrane pore formed by multiple melittin peptides during the simulation. A value of the pore radius was calculated to be within experimental uncertainty. Interestingly, for the system at P/L ≒ 1/26, we observed lipid extraction from the membrane induced by melittin. These results indicate that there are several different modes of the melittin antimicrobial actions depending of the P/L ratio.

Coarse-grained molecular dynamics simulations of melittin antimicrobial actions on lipid membranes

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.