Designing a cross-disciplinary hit-to-lead platform for identifying optimum peptide-based antimicrobial therapeutics

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Antimicrobial peptides (AMPs) are a potential alternative to classical antibiotics that are yetto achieve a therapeutic breakthrough for treatment of systemic infections. We will develop ahit-to-lead platform, with throughput enhanced by high-performance computing, to identifylead candidate peptides with greater potency and selectivity. This lead will have a greater invivo therapeutic index, which will be evaluated through biophysical and biochemicalexperimental approaches. We will then use this platform to investigate the synergistic effectsof a combination of these leads in order to determine the best 'cocktail' of therapeutics whentargeting either Gram-positive or Gram-negative bacteria.