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


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. An Ile1Trp mutation of the N-terminus of nisin has been modelled and docked onto lipid II models; the computed binding affinity increased compared to wild-type. 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. Nisin(2) inserts into the membrane and we propose this as 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.

SUBMITTER: Mulholland S 

PROVIDER: S-EPMC4758073 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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

Mulholland Sam S   Turpin Eleanor R ER   Bonev Boyan B BB   Hirst Jonathan D JD  

Scientific reports 20160218


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 bu  ...[more]

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