Structural-dynamic Model of the Complex of the Shortened Analog of the Lantibiotic Nisin with Its Target-lipid Fragment II

Purposeful blocking the work of the lipid II molecule, involved in the bacterial cell wall biosynthesis pathway, can disrupt this process and lead to bacterial cell death. The most promising candidate for the development of new drugs acting on lipid II is lantibiotic nisin. Using NMR spectroscopy, the motif of binding to the target in DMSO was established, whereas in real conditions, i.e. on the bacterial membrane surface, the structure of the complex remains unknown. Investigation of the nisin/lipid II system using computer simulation methods is an important step towards understanding the mechanism of molecular interaction. In this work, the method of molecular dynamics was used to find the conformation of lantibiotic, in which nisin is most effectively interacting with lipid IIs, comparable to that found in NMR experiments by the number of formed intermolecular hydrogen bonds. The parameters characterizing structure are defined and described. It was shown that the presence of target molecules in the solution stabilize this conformation. The dependence of the complex structure on the environment has been revealed.