文章基本信息

标题：Mapping the Dynamic Functions and Structural Features of AcrB Efflux Pump Transporter Using Accelerated Molecular Dynamics Simulations
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作者：Shirin Jamshidi ; J. Mark Sutton ; Khondaker Miraz Rahman 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：10470
DOI：10.1038/s41598-018-28531-6
语种：English
出版社：Springer Nature
摘要：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.