To prevent bacterial infections, antibiotics have long stood as the primary shield. However, their widespread and often excessive use has led to the alarming rise of antibiotic resistance (AMR). It is characterized by microorganisms evolving mechanisms to bypass the effect of traditional drugs and is widely considered as a global health threat. Among the alternative antimicrobial strategies antimicrobial peptides (AMPs) are the most promising candidates. They are small multifunctional proteins that exhibit broad-spectrum activity against bacteria, viruses, fungi, and even cancer cells. In this study, we focus on dendropsophin 1 (Dc1), a novel AMP extracted from the skin of Dendropsophus columbianus , along with its two analogs, Dc1.1 and Dc1.2. While their antimicrobial efficacy has been experimentally demonstrated by Triana-Vidal et al, the underlying molecular mechanisms remain poorly understood. Using molecular dynamics (MD) simulations, we investigated the interaction of these peptides with a model Gram-positive bacterial membrane. In order to predict the potentials of all three peptides, we have analyzed their stability and secondary structures that align with the experimental evidence. After exploring both parallel and transmembrane configuration, our results reveal effective interactions that leads to notable peptide-induced membrane disruption. Furthermore, we have found small toroidal pores that transport water molecules between the extracellular environment and the cytosolic region of the bacterial membrane. This study provides molecular insights into the peptide-membrane interface, supporting the potential of AMPs as next-generation therapeutics against resistant pathogens.
Hossen et al. (2026) studied this question.