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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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 |
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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 |
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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. |
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School of Chemical and Biomedical Engineering |
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School of Chemical and Biomedical Engineering Liu, Yang Liu, Yaxin Chan-Park, Mary Bee Eng Mu, Yuguang |
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Article |
author |
Liu, Yang Liu, Yaxin Chan-Park, Mary Bee Eng Mu, Yuguang |
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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 |
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Binding modes of teixobactin to lipid ii : molecular dynamics study |
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Binding modes of teixobactin to lipid ii : molecular dynamics study |
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binding modes of teixobactin to lipid ii : molecular dynamics study |
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2018 |
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https://hdl.handle.net/10356/89633 http://hdl.handle.net/10220/44991 |
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