Determining the membrane location of rationally designed antimicrobial peptides (AMPs) with lipid model membranes (LMMs)__

In an effort to thwart the world-wide growing bacterial resistance to current antibiotics, we are studying the structure and function of five novel antimicrobial peptides (AMPs) that are rationally designed using three types of amino acids; we vary peptide chain length, charge, hydrophobicity, hydrophobic moment and secondary structure. These AMPs selectively attack the bacterial membrane rather than a metabolic pathway and so are slower to incur bacterial resistance. We need neutron reflectivity data to precisely locate the peptides in lipid model membranes (LMMs) mimicking Gram-negative and Gram-positive bacteria, and eukaryotic cells. When positional data from NR is combined with membrane thickness data from X-ray diffuse scattering (XDS), we can then compare our structural data to that from molecular dynamics simulators to obtain angstrom-level information about amino acid locations in the membrane. This structural information is required to formulate a hypothesis regarding the mechanism of bacterial killing by AMPs which will guide future AMP synthesis and testing.