Molecular Dynamics Simulations of Inwardly Rectifying (Kir) Potassium Channels:
A Comparative Study<sup>†</sup>
Shozeb Haider
Syma Khalid
Stephen J. Tucker
Frances M. Ashcroft
Mark S. P. Sansom
10.1021/bi062210f.s002
https://acs.figshare.com/articles/journal_contribution/Molecular_Dynamics_Simulations_of_Inwardly_Rectifying_Kir_Potassium_Channels_A_Comparative_Study_sup_sup_/3016897
Inward rectifier potassium (Kir) channels regulate cell excitability and transport K<sup>+</sup> ions across
membranes. Homotetrameric models of three mammalian Kir channels (Kir1.1, Kir3.1, and Kir6.2) have
been generated, using the KirBac3.1 transmembrane and rat Kir3.1 intracellular domain structures as
templates. All three models have been explored by 10 ns molecular dynamics simulations in phospholipid
bilayers. Analysis of the initial structures revealed conservation of potential lipid interaction residues
(Trp/Tyr and Arg/Lys side chains near the lipid headgroup−water interfaces). Examination of the
intracellular domains revealed key structural differences between Kir1.1 and Kir6.2 which may explain
the difference in channel inhibition by ATP. The behavior of all three models in the MD simulations
revealed that they have conformational stability similar to that seen for comparable simulations of, for
example, structures derived from cryoelectron microscopy data. Local distortions of the selectivity filter
were seen during the simulations, as observed in previous simulations of KirBac and in simulations and
structures of KcsA. These may be related to filter gating of the channel. The intracellular hydrophobic
gate does not undergo any substantial changes during the simulations and thus remains functionally closed.
Analysis of lipid−protein interactions of the Kir models emphasizes the key role of the M0 (or “slide”)
helix which lies approximately parallel to the bilayer−water interface and forms a link between the
transmembrane and intracellular domains of the channel.
2007-03-27 00:00:00
rat Kir 3.1 intracellular domain structures
Molecular Dynamics Simulations
lipid interaction residues
MD
simulation
intracellular domains
KirBac 3.1 transmembrane
ATP
cryoelectron microscopy data
model