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Thermodynamic integration network approach to ion transport through protein channels: Perspectives and limits
Author(s) -
Na Sehee,
Steinbrecher Thomas,
Koslowski Thorsten
Publication year - 2018
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.25615
Subject(s) - thermodynamic integration , molecular dynamics , ion , chemistry , head (geology) , solvation , gramicidin , chemical physics , thermodynamics , physics , computational chemistry , biochemistry , organic chemistry , geomorphology , membrane , geology
We present a molecular dynamics simulation study of alkali metal cation transport through the double‐helical and the head‐to‐head conformers of the gramicidin ion channel. Our approach is based on a thermodynamic integration network, which consists of a sequence of transport reactions, absolute free energies of solvation and cycles of alchemical transmutations of the ions. In this manner, we can reliably estimate free energies and their statistical errors via a least‐squares method without imposing external forces on the system. Within the double helical channel, we find a free energy surface typical for hopping transport between isoenergetic sites of ion localization, separated by comparatively large activation barriers. For fast transport through the head‐to‐head conformation, the thermodynamic network scheme starts to break down. © 2018 Wiley Periodicals, Inc.