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

Scientific Reports
Sam MulhollandJonathan D Hirst

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 lipi...Continue Reading

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Citations

Jul 23, 2019·Omics : a Journal of Integrative Biology·Sameeksha Tiwari, Upendra N Dwivedi
Jun 3, 2020·Scientific Reports·Irina PaninaAnton Chugunov
Oct 12, 2020·FEBS Letters·Sander H J SmitsKonstantinos Beis
Jan 1, 2019·Comprehensive Reviews in Food Science and Food Safety·Gang ChenOsvaldo H Campanella
Apr 3, 2020·Journal of Molecular Biology·Sean D Workman, Natalie C J Strynadka
Mar 28, 2021·Computational Biology and Chemistry·Ramanathan NivethaSundaram Janarthanan
Dec 8, 2021·Journal of Chemical Theory and Computation·Rudramani PokhrelPrem P Chapagain

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Methods Mentioned

BETA
NMR

Software Mentioned

GUI
AutoDockVina
Discovery Studio
NPAT
GROMOS
CHARMM
AutoDockTools
NAMD
AutoDock Vina

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