Local conformational dynamics regulating transport properties of a Cl- /H+ antiporter

J Comput Chem. 2020 Mar 5;41(6):513-519. doi: 10.1002/jcc.26093. Epub 2019 Oct 21.


ClC-ec1 is a Cl- /H+ antiporter that exchanges Cl- and H+ ions across the membrane. Experiments have demonstrated that several mutations, including I109F, decrease the Cl- and H+ transport rates by an order of magnitude. Using reactive molecular dynamics simulations of explicit proton transport across the central region in the I109F mutant, a two-dimensional free energy profile has been constructed that is consistent with the experimental transport rates. The importance of a phenylalanine gate formed by F109 and F357 and its influence on hydration connectivity through the central proton transport pathway is revealed. This work demonstrates how seemingly subtle changes in local conformational dynamics can dictate hydration changes and thus transport properties. © 2019 Wiley Periodicals, Inc.

Keywords: antiporter; free energy sampling; local protein dynamics; molecular dynamics; proton transport.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antiporters / chemistry
  • Antiporters / metabolism*
  • Biological Transport
  • Escherichia coli / chemistry*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / metabolism*
  • Molecular Dynamics Simulation*
  • Protein Conformation
  • Water / chemistry
  • Water / metabolism


  • Antiporters
  • CLC-ec1 protein, E coli
  • Escherichia coli Proteins
  • Water