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Mapping the Dynamic Functions and Structural Features of AcrB Efflux Pump Transporter Using Accelerated Molecular Dynamics Simulations

Multidrug efflux pumps confer resistance to their bacterial hosts by pumping out a diverse range of compounds, including most antibiotics. Being more familiar with the details of functional dynamics and conformations of these types of pumps could help in discovering approaches to stop them functioni...

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Autores principales: Jamshidi, Shirin, Sutton, J. Mark, Rahman, Khondaker Miraz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041327/
https://www.ncbi.nlm.nih.gov/pubmed/29992991
http://dx.doi.org/10.1038/s41598-018-28531-6
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author Jamshidi, Shirin
Sutton, J. Mark
Rahman, Khondaker Miraz
author_facet Jamshidi, Shirin
Sutton, J. Mark
Rahman, Khondaker Miraz
author_sort Jamshidi, Shirin
collection PubMed
description Multidrug efflux pumps confer resistance to their bacterial hosts by pumping out a diverse range of compounds, including most antibiotics. Being more familiar with the details of functional dynamics and conformations of these types of pumps could help in discovering approaches to stop them functioning properly. Computational approaches, particularly conventional molecular dynamics simulations followed by diverse post simulation analysis, are powerful methods that help researchers by opening a new window to study phenomena that are not detectable in as much detail in vitro or in vivo as they are in silico. In this study, accelerated molecular dynamics simulations were applied to study the dynamics of AcrB efflux pump transporters in interaction with PAβN and tetracycline as an inhibitor and a substrate, respectively, to compare the differences in the dynamics and consequently the mechanism of action of the pump. The different dynamics for PAβN -bound form of AcrB compared to the TET-bound form is likely to affect the rotating mechanism typically observed for AcrB transporter. This shows the dynamics of the active AcrB transporter is different in a substrate-bound state compared to an inhibitor-bound state. This advances our knowledge and helps to unravel the mechanism of tripartite efflux pumps.
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spelling pubmed-60413272018-07-13 Mapping the Dynamic Functions and Structural Features of AcrB Efflux Pump Transporter Using Accelerated Molecular Dynamics Simulations Jamshidi, Shirin Sutton, J. Mark Rahman, Khondaker Miraz Sci Rep Article Multidrug efflux pumps confer resistance to their bacterial hosts by pumping out a diverse range of compounds, including most antibiotics. Being more familiar with the details of functional dynamics and conformations of these types of pumps could help in discovering approaches to stop them functioning properly. Computational approaches, particularly conventional molecular dynamics simulations followed by diverse post simulation analysis, are powerful methods that help researchers by opening a new window to study phenomena that are not detectable in as much detail in vitro or in vivo as they are in silico. In this study, accelerated molecular dynamics simulations were applied to study the dynamics of AcrB efflux pump transporters in interaction with PAβN and tetracycline as an inhibitor and a substrate, respectively, to compare the differences in the dynamics and consequently the mechanism of action of the pump. The different dynamics for PAβN -bound form of AcrB compared to the TET-bound form is likely to affect the rotating mechanism typically observed for AcrB transporter. This shows the dynamics of the active AcrB transporter is different in a substrate-bound state compared to an inhibitor-bound state. This advances our knowledge and helps to unravel the mechanism of tripartite efflux pumps. Nature Publishing Group UK 2018-07-11 /pmc/articles/PMC6041327/ /pubmed/29992991 http://dx.doi.org/10.1038/s41598-018-28531-6 Text en © The Author(s) 2018 Open Access 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. The 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/.
spellingShingle Article
Jamshidi, Shirin
Sutton, J. Mark
Rahman, Khondaker Miraz
Mapping the Dynamic Functions and Structural Features of AcrB Efflux Pump Transporter Using Accelerated Molecular Dynamics Simulations
title Mapping the Dynamic Functions and Structural Features of AcrB Efflux Pump Transporter Using Accelerated Molecular Dynamics Simulations
title_full Mapping the Dynamic Functions and Structural Features of AcrB Efflux Pump Transporter Using Accelerated Molecular Dynamics Simulations
title_fullStr Mapping the Dynamic Functions and Structural Features of AcrB Efflux Pump Transporter Using Accelerated Molecular Dynamics Simulations
title_full_unstemmed Mapping the Dynamic Functions and Structural Features of AcrB Efflux Pump Transporter Using Accelerated Molecular Dynamics Simulations
title_short Mapping the Dynamic Functions and Structural Features of AcrB Efflux Pump Transporter Using Accelerated Molecular Dynamics Simulations
title_sort mapping the dynamic functions and structural features of acrb efflux pump transporter using accelerated molecular dynamics simulations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041327/
https://www.ncbi.nlm.nih.gov/pubmed/29992991
http://dx.doi.org/10.1038/s41598-018-28531-6
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