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Local conformational dynamics regulating transport properties of a Cl − /H + antiporter
Author(s) -
Wang Zhi,
Swanson Jessica M. J.,
Voth Gregory A.
Publication year - 2020
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.26093
Subject(s) - antiporter , chemistry , molecular dynamics , dynamics (music) , computational chemistry , physics , membrane , biochemistry , acoustics
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.