How does in-membrane structuring affect antimicrobial efficiency of AMPs?

A short designed antimicrobial peptide (AMP) G(IIKK)3I (GIK) kills pathogenic microbes by disrupting their membranes. Our recent study has revealed that substitution of Ile (I) by Trp (W) or Phe (F), or substitution of Lys (K) by Arg (R) in GIK leads to GWK, GFK and GIR and improves AMP’s antimicrobial performance in terms of antimicrobial efficiency measured by minimum inhibition concentration and dynamic killing measured by minimum contact time to achieve 99.9% killing at a fixed AMP concentration. We hypothesize the efficiency improvement is related to membrane leakage underpinned by AMP binding. We request 3 days of SANS2D time to examine how the 4 AMPs bind small unilamellar vesicles mimicking outer/inner bacterial membranes of E. coli. This experiment is crucial to provide vital data about different in-membrane nanostructures to guide MD simulations and future SANS data analysis.