Docking and molecular dynamics simulations of the ternary complex nisin2:lipid II
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-...
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Nature Publishing Group
2016
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| Online Access: | https://eprints.nottingham.ac.uk/31380/ |
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| author | Mulholland, Sam Turpin, Eleanor R. Bonev, Boyan B. Hirst, J.D. |
| author_facet | Mulholland, Sam Turpin, Eleanor R. Bonev, Boyan B. Hirst, J.D. |
| author_sort | Mulholland, Sam |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:12:13Z |
| format | Article |
| id | nottingham-31380 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:12:13Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
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| spelling | nottingham-313802020-05-04T17:36:31Z https://eprints.nottingham.ac.uk/31380/ Docking and molecular dynamics simulations of the ternary complex nisin2:lipid II Mulholland, Sam Turpin, Eleanor R. Bonev, Boyan B. Hirst, J.D. 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. Nature Publishing Group 2016-02-18 Article PeerReviewed Mulholland, Sam, Turpin, Eleanor R., Bonev, Boyan B. and Hirst, J.D. (2016) Docking and molecular dynamics simulations of the ternary complex nisin2:lipid II. Scientific Reports, 6 (21185). pp. 1-11. ISSN 2045-2322 computational biophysics computational chemistry membrane biophysics http://www.nature.com/articles/srep21185 doi:10.1038/srep21185 doi:10.1038/srep21185 |
| spellingShingle | computational biophysics computational chemistry membrane biophysics Mulholland, Sam Turpin, Eleanor R. Bonev, Boyan B. Hirst, J.D. Docking and molecular dynamics simulations of the ternary complex nisin2:lipid II |
| title | Docking and molecular dynamics simulations of the ternary complex nisin2:lipid II |
| title_full | Docking and molecular dynamics simulations of the ternary complex nisin2:lipid II |
| title_fullStr | Docking and molecular dynamics simulations of the ternary complex nisin2:lipid II |
| title_full_unstemmed | Docking and molecular dynamics simulations of the ternary complex nisin2:lipid II |
| title_short | Docking and molecular dynamics simulations of the ternary complex nisin2:lipid II |
| title_sort | docking and molecular dynamics simulations of the ternary complex nisin2:lipid ii |
| topic | computational biophysics computational chemistry membrane biophysics |
| url | https://eprints.nottingham.ac.uk/31380/ https://eprints.nottingham.ac.uk/31380/ https://eprints.nottingham.ac.uk/31380/ |