Molecular Dynamics Simulations Help Determine the Molecular Mechanisms of Lasioglossin-III and Its Variant Peptides’ Membrane Interfacial Interactions

Lasioglossin-III (LL-III) is a potent broad-spectrum antimicrobial peptide used in diverse antimicrobial applications. In this work, coarse–grained and all-atom molecular dynamics simulation strategies were used in tandem to interpret the molecular mechanisms involved in the interfacial dynamics of LL-III and its recombinant variants during interactions with diverse cell membrane systems. Our results indicate that the membrane charges act as the driving force for initiating the membrane–peptide interactions, while the hydrophobic or van der Waals forces help to reinforce the membrane–peptide bindings. The optimized charge-hydrophobicity ratio of the LL-III peptides helps ensure their high specificity toward bacterial membranes compared to mammalian membrane systems, which also helps explain our experimental observations. Overall, we hope that our work gives new insight into the antimicrobial action of LL-III peptides and that the adopted simulation strategy will help other scientists and engineers extract maximal information from complex molecular simulations using minimal computational power.