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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. March 2005, Volume 4, Number 3, 235-248 |
Analysis of the Sequence KWKWK…K in the KcsA Protein Channel
using Molecular Dynamics Simulations
Céline Boiteux, Mylène Compoint, Philippe Huetz, Christophe Ramseyer, and Claude Girardet
Internet Electron. J. Mol. Des. 2005, 4, 235-248
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Abstract:
In this paper we analyze the electrostatic interactions in the open
and closed states of the KcsA channel. We focus on the stability
of the KWKWK…K sequence already proposed as a model for
the permeation mechanism of the KcsA transmembrane channel.
The fact that the channel can accommodate more than one ion in
the pore is crucial to explain the high diffusion rate of K+ ions
observed. We also address the question of the accuracy of the
force fields by comparing them to ab initio calculations. On the
basis of molecular dynamics calculations, we determine the
electrostatic potential due to the protein embedded in its
membrane using either AMBER6 force fields or quantum
calculations conducted with GAUSSIAN 03 at the HF 6-31G(d)
level. Both force field and quantum approaches show that water
molecules located in the KWKWK…K sequence play a
structuring role for the ions in the filter. When compared to the
closed state situation, the open state conformation of the protein
promotes very different behaviors of K+ and water motions in the
hydrophobic cavity and in the external mouth of the channel.
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