Thermodynamics of ion binding and occupancy in potassium channels†


Journal article


Zhifeng Jing, Joshua A. Rackers, L. Pratt, Chengwen Liu, S. Rempe, Pengyu Y. Ren
Chemical Science, 2021

Semantic Scholar DOI PubMedCentral PubMed
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APA   Click to copy
Jing, Z., Rackers, J. A., Pratt, L., Liu, C., Rempe, S., & Ren, P. Y. (2021). Thermodynamics of ion binding and occupancy in potassium channels†. Chemical Science.


Chicago/Turabian   Click to copy
Jing, Zhifeng, Joshua A. Rackers, L. Pratt, Chengwen Liu, S. Rempe, and Pengyu Y. Ren. “Thermodynamics of Ion Binding and Occupancy in Potassium Channels†.” Chemical Science (2021).


MLA   Click to copy
Jing, Zhifeng, et al. “Thermodynamics of Ion Binding and Occupancy in Potassium Channels†.” Chemical Science, 2021.


BibTeX   Click to copy

@article{zhifeng2021a,
  title = {Thermodynamics of ion binding and occupancy in potassium channels†},
  year = {2021},
  journal = {Chemical Science},
  author = {Jing, Zhifeng and Rackers, Joshua A. and Pratt, L. and Liu, Chengwen and Rempe, S. and Ren, Pengyu Y.}
}

Abstract

Potassium channels modulate various cellular functions through efficient and selective conduction of K+ ions. The mechanism of ion conduction in potassium channels has recently emerged as a topic of debate. Crystal structures of potassium channels show four K+ ions bound to adjacent binding sites in the selectivity filter, while chemical intuition and molecular modeling suggest that the direct ion contacts are unstable. Molecular dynamics (MD) simulations have been instrumental in the study of conduction and gating mechanisms of ion channels. Based on MD simulations, two hypotheses have been proposed, in which the four-ion configuration is an artifact due to either averaged structures or low temperature in crystallographic experiments. The two hypotheses have been supported or challenged by different experiments. Here, MD simulations with polarizable force fields validated by ab initio calculations were used to investigate the ion binding thermodynamics. Contrary to previous beliefs, the four-ion configuration was predicted to be thermodynamically stable after accounting for the complex electrostatic interactions and dielectric screening. Polarization plays a critical role in the thermodynamic stabilities. As a result, the ion conduction likely operates through a simple single-vacancy and water-free mechanism. The simulations explained crystal structures, ion binding experiments and recent controversial mutagenesis experiments. This work provides a clear view of the mechanism underlying the efficient ion conduction and demonstrates the importance of polarization in ion channel simulations.


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