Binding modes of teixobactin to lipid ii : molecular dynamics study

Teixobactin (TXB) is a newly discovered antibiotic targeting the bacterial cell wall precursor Lipid II (LII). In the present work, four binding modes of TXB on LII were identified by a contact-map based clustering method. The highly flexible binary complex ensemble was generated by parallel temperi...

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Main Authors: Liu, Yang, Liu, Yaxin, Chan-Park, Mary Bee Eng, Mu, Yuguang
Other Authors: School of Chemical and Biomedical Engineering
Format: Article
Language:English
Published: 2018
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Online Access:https://hdl.handle.net/10356/89633
http://hdl.handle.net/10220/44991
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-896332023-02-28T16:58:15Z Binding modes of teixobactin to lipid ii : molecular dynamics study Liu, Yang Liu, Yaxin Chan-Park, Mary Bee Eng Mu, Yuguang School of Chemical and Biomedical Engineering School of Biological Sciences Centre for Antimicrobial Bioengineering Protein Function Predictions Computational Models Teixobactin (TXB) is a newly discovered antibiotic targeting the bacterial cell wall precursor Lipid II (LII). In the present work, four binding modes of TXB on LII were identified by a contact-map based clustering method. The highly flexible binary complex ensemble was generated by parallel tempering metadynamics simulation in a well-tempered ensemble (PTMetaD-WTE). In agreement with experimental findings, the pyrophosphate group and the attached first sugar subunit of LII are found to be the minimal motif for stable TXB binding. Three of the four binding modes involve the ring structure of TXB and have relatively higher binding affinities, indicating the importance of the ring motif of TXB in LII recognition. TXB-LII complexes with a ratio of 2:1 are also predicted with configurations such that the ring motif of two TXB molecules bound to the pyrophosphate-MurNAc moiety and the glutamic acid residue of one LII, respectively. Our findings disclose that the ring motif of TXB is critical to LII binding and novel antibiotics can be designed based on its mimetics. MOE (Min. of Education, S’pore) Published version 2018-06-07T07:18:39Z 2019-12-06T17:29:56Z 2018-06-07T07:18:39Z 2019-12-06T17:29:56Z 2017 Journal Article Liu, Y., Liu, Y., Chan-Park, M. B. E., & Mu, Y. (2017). Binding Modes of Teixobactin to Lipid II: Molecular Dynamics Study. Scientific Reports, 7(1), 17197-. 2045-2322 https://hdl.handle.net/10356/89633 http://hdl.handle.net/10220/44991 10.1038/s41598-017-17606-5 en Scientific Reports © 2017 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. 12 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Protein Function Predictions
Computational Models
spellingShingle Protein Function Predictions
Computational Models
Liu, Yang
Liu, Yaxin
Chan-Park, Mary Bee Eng
Mu, Yuguang
Binding modes of teixobactin to lipid ii : molecular dynamics study
description Teixobactin (TXB) is a newly discovered antibiotic targeting the bacterial cell wall precursor Lipid II (LII). In the present work, four binding modes of TXB on LII were identified by a contact-map based clustering method. The highly flexible binary complex ensemble was generated by parallel tempering metadynamics simulation in a well-tempered ensemble (PTMetaD-WTE). In agreement with experimental findings, the pyrophosphate group and the attached first sugar subunit of LII are found to be the minimal motif for stable TXB binding. Three of the four binding modes involve the ring structure of TXB and have relatively higher binding affinities, indicating the importance of the ring motif of TXB in LII recognition. TXB-LII complexes with a ratio of 2:1 are also predicted with configurations such that the ring motif of two TXB molecules bound to the pyrophosphate-MurNAc moiety and the glutamic acid residue of one LII, respectively. Our findings disclose that the ring motif of TXB is critical to LII binding and novel antibiotics can be designed based on its mimetics.
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Liu, Yang
Liu, Yaxin
Chan-Park, Mary Bee Eng
Mu, Yuguang
format Article
author Liu, Yang
Liu, Yaxin
Chan-Park, Mary Bee Eng
Mu, Yuguang
author_sort Liu, Yang
title Binding modes of teixobactin to lipid ii : molecular dynamics study
title_short Binding modes of teixobactin to lipid ii : molecular dynamics study
title_full Binding modes of teixobactin to lipid ii : molecular dynamics study
title_fullStr Binding modes of teixobactin to lipid ii : molecular dynamics study
title_full_unstemmed Binding modes of teixobactin to lipid ii : molecular dynamics study
title_sort binding modes of teixobactin to lipid ii : molecular dynamics study
publishDate 2018
url https://hdl.handle.net/10356/89633
http://hdl.handle.net/10220/44991
_version_ 1759858099280150528