Magnetic resonance studies of antimicrobial peptides in membranes

The development of microbial resistance to common small molecule antibiotics is continuing to be a thread to modern medicine and drives the search for novel antibiotics for the clinic. Antimicrobial peptides (AMPs), part of the innate immune system, are versatile and show multifaceted antimicrobial activity that has attracted recent focus as only limited cases of resistance are reported to date. AMPs primarily develop their potency at the pathogenic membrane, where they adapt different modes of action that compromise membrane integrity and result in cell death. While the primary peptide structure and overall biophysical characteristics are important for AMP activity, a precise structure–function relationship is still unresolved. The destructive membrane-activity and large conformational space exploited by AMPs is a challenge for biophysical characterisation and typically a battery of different techniques is required to study precise AMP activity. Magnetic resonance methods are outlined and reviewed that span the relevant time scales of the highly dynamic peptide–membrane interaction in a native-like environment. An overview of electron paramagnetic resonance (EPR) and uniaxially oriented nuclear magnetic resonance (NMR) methodologies is presented, which in combination resolve the peptide–lipid interaction in detail; understanding of the bilateral relationship of lipids and peptides is essential for the precise characterisation of native and synthetic AMP sequences.