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@ARTICLE{Bucher:201273,
author = {Bucher, Denis and Guidoni, Leonardo and Carloni, Paolo and
Rothlisberger, Ursula},
title = {{C}oordination {N}umbers of {K}+ and {N}a+ {I}ons {I}nside
the {S}electivity {F}ilter of the {K}cs{A} {P}otassium
{C}hannel: {I}nsights from {F}irst {P}rinciples
{M}olecular {D}ynamics},
journal = {Biophysical journal},
volume = {98},
number = {10},
issn = {0006-3495},
address = {New York, NY},
publisher = {Rockefeller Univ. Press},
reportid = {FZJ-2015-03578},
pages = {L47 - L49},
year = {2010},
abstract = {Quantum mechanics/molecular mechanics (QM/MM)
Car-Parrinello simulations were performed to estimate the
coordination numbers of K+ and Na+ ions in the selectivity
filter of the KcsA channel, and in water. At the DFT/BLYP
level, K+ ions were found to display an average coordination
number of 6.6 in the filter, and 6.2 in water. Na+ ions
displayed an average coordination number of 5.2 in the
filter, and 5.0 in water. A comparison was made with the
average coordination numbers obtained from using classical
molecular dynamics (6.7 for K+ in the filter, 6.6 for K+ in
water, 6.0 for Na+ in the filter, and 5.2 for Na+ in water).
The observation that different coordination numbers were
displayed by the ions in QM/MM simulations and in classical
molecular dynamics is relevant to the discussion of
selectivity in K-channels.Potassium channels are membrane
proteins that can catalyze K+ ions permeation across
cellular membranes while simultaneously discriminating the
permeation of Na+ ions by several orders of magnitude. To
uncover the mechanism of K-channel selectivity in
theoretical studies, the KcsA channel has proved to be a
particularly useful system, because it is relatively small,
and it contains the essential structural elements that are
shared by all potassium channels (1). The selectivity of the
KcsA channel is believed to originate from the conserved
TVGYG signature sequence, which forms a narrow constriction
in the tetrameric pore called the selectivity filter (Fig.
1). The K+/Na+ selectivity in the KcsA channel was initially
proposed to arise from the geometrical arrangement of
ligands in the filter (1), the so-called snug-fit
hypothesis. However, molecular dynamics (MD) simulations
have shown that the selectivity filter is relatively
flexible and that Na+ ions are able to interact with the
carbonyl ligands that pave the interior of the selectivity
filter (2). This leads to the idea that other interactions,
such as the repulsion between carbonyl groups, play an
important role in the selectivity (3). In addition, the
selectivity has been discussed as arising from the favorable
arrangement of the carbonyl in the filter, which may promote
high coordination numbers, compared to the ion coordination
numbers in water (4 and 22).},
cin = {GRS / IAS-5},
ddc = {570},
cid = {I:(DE-Juel1)GRS-20100316 / I:(DE-Juel1)IAS-5-20120330},
pnm = {899 - ohne Topic (POF2-899)},
pid = {G:(DE-HGF)POF2-899},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000277858400001},
pubmed = {pmid:20483308},
doi = {10.1016/j.bpj.2010.01.064},
url = {https://juser.fz-juelich.de/record/201273},
}