Docking and molecular dynamics simulations of the ternary complex nisin2:lipid II

Mulholland, Sam; Turpin, Eleanor R.; Bonev, Boyan B.; Hirst, J.D.

Abstract

Lanthionine antibiotics are an important class of naturally-occurring antimicrobial peptides. The best-known, nisin, is a commercial food preservative. However, structural and mechanistic details on nisin/lipid II membrane complexes are currently lacking. Recently, we have developed empirical force-field parameters to model lantibiotics. Docking and molecular dynamics (MD) simulations have been used to study the nisin2:lipid II complex in bacterial membranes, which has been put forward as the building block of nisin/lipid II binary membrane pores. A Ile1Trp mutation of the N-terminus of nisin has been modelled and docked onto lipid II models; the computed binding affinity increased compared to wildtype. Wild-type nisin was also docked onto three different lipid II structures and a stable 2:1 nisin:lipid II complex formed. This complex was inserted into a membrane. Six independent MD simulations revealed key interactions in the complex, specifically the N terminal engagement of nisin with lipid II at the pyrophosphate and C-terminus of the pentapeptide chain. Nisin2 inserts into the membrane and we propose this is the first step in pore formation, mediated by the nisin N-terminus–lipid II pentapeptide hydrogen bond. The lipid II undecaprenyl chain adopted different conformations in the presence of nisin, which may also have implications for pore formation.

Citation

Mulholland, S., Turpin, E. R., Bonev, B. B., & Hirst, J. (2016). Docking and molecular dynamics simulations of the ternary complex nisin2:lipid II. Scientific Reports, 6(21185), https://doi.org/10.1038/srep21185

• Journal Article Type: Article
• Publication Date: Feb 18, 2016
• Deposit Date: Feb 19, 2016
• Publicly Available Date: Feb 19, 2016
• Journal: Scientific Reports
• Electronic ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 21185
• DOI: https://doi.org/10.1038/srep21185
• Keywords: computational biophysics, computational chemistry, membrane biophysics
• Public URL: https://nottingham-repository.worktribe.com/output/775877
• Publisher URL: http://www.nature.com/articles/srep21185