Lipid-II forms potential “landing terrain” for lantibiotics in simulated bacterial membrane

Scientific Reports. 2013. Vol. 3. No. 1678.

Chugunov A. O., Pyrkova D. V., Nolde D. E., Polyansky A. A., Pentkovsky V. M., Ефремов Р. Г.

Bacterial cell wall is targeted by many antibiotics. Among them are lantibiotics, which realize their function via interaction with transmembrane lipid-II molecule — a chemically conserved part of the cell wall synthesis pathway. To investigate structural and dynamic properties of this molecule, we have performed a series of nearly microsecond-long molecular dynamics simulations (MD) of lipid-II and some of its analogs in zwitterionic single component and charged mixed model phospholipid bilayers (the reference and mimic of the bacterial plasmatic membrane, respectively). Extensive analysis revealed that lipid-II forms a unique “amphiphilic pattern” exclusively on the surface of the model bacterial membrane (and not in the reference bilayer). We hypothesize that conserved features of lipid-II along with characteristic modulation of the bacterial membrane provide a recognition spot for many lantibiotics. This putative recognition mechanism opens new opportunities for studies on lantibiotics action and design of novel armament against resistant bacterial strains.

Ключевые слова: компьютерные модели, Computational models, Computational biophysics, Biomolecular conformation, Membrane lipids, вычислительная биофизика, конформация биомолекул, мембранные липиды