Figure 10

Molecular dynamics simulation of coexistence Mg²⁺ and SPM action in the WT Kir2.1 channel pore.

(a) In the presence of approximately forty water molecules, one Mg²⁺, one SPM molecules and seven K⁺ ions are applied to the central cavity region of the WT Kir2.1 channel. The Mg²⁺ (colored are yellow) and SPM molecules (hydrogen atoms are colored grayish white; carbon, black; and nitrogen, blue) of the blocking sites are presented in a CPK model. The representative structure of the cytoplasmic and transmembrane domains of one subunit of the WT Kir2.1 channel is shown. A regional view of the residues T141, S165 and D172 is shown in the boxed panel. The side chains of T141, S165 and D172 are shown in CPK model and the hydrogen atoms are colored grayish white; nitrogen, blue; oxygen, red; and carbon, black. All of the other atoms in the channel protein are colored green. (b) With the same approaches as that in part a two subunits of the channel are presented in a solid–ribbon model. The distance between diagonal residues D172 from tip to tip is profoundly decreased (~9.7 Å) in the coexistence presence of Mg²⁺ and SPM, but not in presence of Mg²⁺ (~17.3 Å) or SPM alone (~15.5 Å). Note that Mg²⁺ is located close to S165 whereas SPM is located close to D172. (c) A summary plot of the tip–to–tip diagonal distance between sites D172 in control and in the presence of SPM, or Mg²⁺, or both, in the WT Kir2.1 channel pore. Note that an evident narrowing occurs only in the concomitant presence of Mg²⁺ and SPM. (d) A summary plot of the diagonal (tip–to–tip) distances between residues T141, S165 and D172 in control (no blockers) and in the concomitant presence of Mg²⁺ and SPM in the Kir2.1 channel pore. Note that an evident narrowing occurs only at the level of D172, but not at T141 and S165.