Molecular dynamic studies of the antimicrobial peptide Dermaseptin B2 and its derivative Dermaseptin DS01

Rapid development of resistance to antimicrobials and the lack of new therapy development are critical issues facing infectious disease treatment globally. Over the past two decades, antimicrobial peptides (AMPs) have been extensively researched and shown to exhibit broad-spectrum activity against various microbes, viruses, fungi and even cancerous cells, thus they are thought to have the solution to the increasing resistance problem. Understanding the role that antimicrobial peptides play in preventing infections is essential if these peptides are to form a new class of clinically effective antimicrobial agents and for them to be used therapeutically in humans. This research will look at a family of antimicrobial peptides known as Dermaseptin that are secreted by an Amazonian frog species. These peptides have shown potent activity against Gram-negative and positive bacteria, viruses, fungi and cancer cells. They exhibit bacterial colony inhibition effect at the micromolar concentration level with minimal effect on host cells. For its high potency and lack of toxicity to host cell, the Dermaseptin family appears to have therapeutic potential and this thesis will attempt to understand how they interact with membranes at the molecular level using coarse-grained computational models and simulations