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

Z Wang and JMJ Swanson and GA Voth, JOURNAL OF COMPUTATIONAL CHEMISTRY, 41, 513-519 (2020).

DOI: 10.1002/jcc.26093

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. (c) 2019 Wiley Periodicals, Inc.

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