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Gating energetics of a voltage‐dependent K + channel pore domain
Author(s) -
Starek Greg,
Freites J. Alfredo,
Bernèche Simon,
Tobias Douglas J.
Publication year - 2017
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.24742
Subject(s) - gating , energy landscape , maxima and minima , umbrella sampling , molecular dynamics , chemical physics , chemistry , voltage , potential energy , potassium channel , domain wall (magnetism) , domain (mathematical analysis) , potential of mean force , molecular physics , computational chemistry , biophysics , physics , atomic physics , mathematical analysis , biochemistry , mathematics , magnetization , quantum mechanics , magnetic field , biology
We used targeted molecular dynamics, informed by experimentally determined inter‐atomic distances defining the pore region of open and closed states of the KvAP voltage‐gated potassium channel, to generate a gating pathway of the pore domain in the absence of the voltage‐sensing domains. We then performed umbrella sampling simulations along this pathway to calculate a potential of mean force that describes the free energy landscape connecting the closed and open conformations of the pore domain. The resulting energetic landscape displays three minima, corresponding to stable open, closed, and intermediate conformations with roughly similar stabilities. We found that the extent of hydration of the interior of the pore domain could influence the free energy landscape for pore opening/closing. © 2017 Wiley Periodicals, Inc.