Peptidoglycan-targeting antimicrobial peptides are presently under-utilized in bacterial management and resistance remains uncommon, yet these compounds hold much promise and may offer routes to novel strategies for bacterial control. The management of Gram-negative bacteria is particularly problematic as they are encapsulated in a protective lipopolysaccharide (LPS) layer. The LPS molecule contains a lipid moiety, lipid A, a core polysaccharide region, which is extensively phosphorylated and pyrophosphorylated and an outer polysaccharide O-antigen region. LPS presents a major barrier to pharmacological control of Gram-negatives. A commercially developed and well-characterised lantibiotic, nisin, is produced by the Gram-positive bacterium Lactococcus lactis and is effective against Staphylococci, Clostridia and Lysteria. Currently having numerous applications in food protection worldwide, nisin is a non-toxic and highly effective antimicrobial, which targets pyrophosphate-derivatised peptidoglycan intermediates. We hypothesise that pyrophosphorylated saccharides in the LPS core region present viable targets for recognition by chemotherapeutic agents and can serve as templates for antimicrobial design. We propose a computational study of the interactions between an established antimicrobial compound and LPS and to verify experimentally the interaction using solid state NMR. At a functional level, we will assess the stability of lipid membranes without or with LPS when incubated with membrane-disrupting antimicrobial peptide nisin. Resistance to antibiotics and the spread of infectious diseases in a globalised society present significant challenges to infection management and disease control. The development of new antibacterial compounds, which exploit previously undeveloped specific bacterial targets remains of prime interest in antimicrobial drug design. We hypothesise that a lipopolysaccharide (LPS) protective layer, present in some particularly challenging organisms, presents viable molecular targets for antibacterial drug design. We will use high performance computing tools to investigate molecular complexes between LPS and a well-known antimicrobial, nisin (E234). The computational analysis will provide templates for antimicrobial design. We seek experimental verification of the existence of such complexes by following changes in LPS molecular motions by nuclear magnetic resonance (NMR). We also propose that LPS facilitates the disruption of lipid membranes by nisin and will test this hypothesis using fluorescence spectroscopy.