Key result
Multiscale Kir2.1 modeling reveals specific magnesium and spermine binding sites en route to the cavity.
Multiscale modeling identifies specific amino acid residues (Glu299, Asp255, Glu224) as key interaction sites for magnesium and spermine in the Kir2.1 potassium channel, providing mechanistic insight into its inward-rectifying behavior.
The Kir2.1 potassium channel owes its inward-rectifying behavior to blocking by multivalent ions, e.g., magnesium and spermine, which access the channel from the cytoplasm and are thought to bind within the pore. To investigate the pathway followed by these ions from the cytoplasm through the pore, we have used multiscale modeling (via continuum electrostatics calculations, docking, and molecular dynamics simulations) to identify possible binding sites en route. On its way to eventually binding in the cavity, magnesium interacts extensively with Glu299, which lines the pore in the center of the intracellular domain. Interaction sites for spermine are formed by Asp255, Glu299, and Glu224. Entropic factors seem to favor interactions of spermine within the center of the cytoplasmic domain.
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Tai et al. (2009) studied Kir2.1 potassium channel inward-rectifying behavior. Multiscale modeling was evaluated on Ion binding sites en route to the cavity. Multiscale modeling of the Kir2.1 channel revealed that magnesium interacts with Glu299, while spermine interacts with Asp255, Glu299, and Glu224 en route to the cavity.
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