Turn off MathJax
Article Contents
Yun Huang, Hao-chen Xu, Jie-Lou Liao. Coarse-Grained Free-Energy Simulations of Conformational State Transitions in an ABC Exporter[J]. Chinese Journal of Chemical Physics .
Citation: Yun Huang, Hao-chen Xu, Jie-Lou Liao. Coarse-Grained Free-Energy Simulations of Conformational State Transitions in an ABC Exporter[J]. Chinese Journal of Chemical Physics .

Coarse-Grained Free-Energy Simulations of Conformational State Transitions in an ABC Exporter

  • Accepted Date: 2020-07-02
  • Available Online: 2019-09-01
  • ATP-binding cassette (ABC) exporters transport many substrates out of cellular membranes via alternating between inward-facing (IF) and outward-facing (OF) conformations. Despite extensive research efforts over the past decades, understanding of the molecular mechanism remains elusive. As these large-scale conformational movements are global and collective, we have previously performed extensive coarse-grained molecular dynamics (CG-MD) simulations of the potential of mean force (PMF) along the conformational transition pathway [Z. Wang et. al JPCB, 119, 1295?1301 (2015)]. However, the occluded (OC) conformational state, in which both the internal and external gate are closed, was not determined in the calculated free energy profile. In this paper, we extend the above methods to the calculation of the free energy profile along the reaction coordinate, d1- d2, which are the COM distances between the two sides of the internal (d1) and the external gate (d2). The PMF is thus obtained to identify the transition pathway, along which several OF-, IF- and OC- state structures are predicted in good agreement with structural experiments. Our CG-MD free-energy simulations demonstrate that the internal gate is closed before the external gate is open during the IF to OF transition and vice versa during the IF to OF transition. Our results capture the unidirectional feature of substrate translocation via the exporter, which is functionally important in biology. This finding is different from the results, in which both the internal and external gates are open reported in an X-ray experiment [Ward A. et al, PNAS, 104, 19005?19010 (2007)]. Our study sheds light on the molecular mechanism of the state transitions in the ABC exporter.

     

  • loading
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (688) PDF downloads(35) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return