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. 2018 Jun;9(6):580-585.
doi: 10.1007/s13238-018-0522-y.

Simulating the ion permeation and ion selection for a eukaryotic voltage-gated sodium channel NaVPaS

Juanrong Zhang #  1   2 , Wenzhi Mao #  1   2 , Yanhui Ren #  1   2 , Rui-Ning Sun  1   2 , Nieng Yan  3   4 , Haipeng Gong  5   6
Affiliations

Simulating the ion permeation and ion selection for a eukaryotic voltage-gated sodium channel NaVPaS

Juanrong Zhang et al. Protein Cell. 2018 Jun.
No abstract available

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Figures

Figure 1
Figure 1
Na + ions prefer to permeate in an asymmetric manner whereas K + ions are reluctant to enter the SF of Na V Pas. (A) Structure of the PD of NaVPaS. The side chains of residue Glu704 as well as the DEKA residues (Asp375, Glu701, Lys1061 and Ala1353) are shown as sticks. Four homologous repeats (I–IV) are colored in grey, yellow, green and cyan, respectively. (B) Probability distributions of Na+ and K+ ions residing in the SF. Boundaries of the DEKA region are labeled by red dotted lines. (C and D) Time-dependent ion trails of Na+ (C) and K+ (D) ions. Trails of ions that have ever entered the DEKA region are displayed in different colors to distinguish the ion identity, while the others are shown in grey. (E) 3D probability density map as well as the contour envelops (in orange wireframes) are obtained from the positions of Na+ ions that entered the SF of NaV channels. (F) Top views of the contour envelopes of probability density map covering 90%, 80%, 70% and 60% of density points in NaVPaS. (G) Top views of the contour envelopes of probability density map covering 90%, 80%, 70% and 60% of density points in NaVRh
Figure 2
Figure 2
Calculations along the most probable ion permeation path imply the origin of Na + /K + selectivity in Na V Pas. (A) The permeation path (red curve) of Na+ ions from the extracellular bulk to the central cavity identified by the 3D ridge detection algorithm. Only P-loops of homologous repeats I-III are shown for clarity. (B) The PMF profile along the identified permeation path. Three interesting windows in the umbrella sampling calculations are labeled as a, b and c on the curve, with representative structures shown aside. Representative structures of these three windows as well as a reference window (labeled as ref) were chosen for free energy perturbation calculations. (C) The probability density function of Na+ coordination by Glu704 (green), Asp375 (red) and Glu701 (blue) in all windows of the umbrella sampling calculations, respectively. Relationship between window Z-coordinates and reaction coordinates is shown in Fig. S7. (D and E) Time-dependent ion trails of Na+ (D) and K+ (E) ions in the DEAA derivate. Boundaries of the DEAA region (red dotted lines) were estimated in a similar approach to Fig. S4A and S4B. Trails of ions that have ever entered the DEAA region are displayed in different colors to distinguish the ion identity, while the others are shown in grey. (F) Top views of the probability density maps of Na+ ions in the DEAA (left) and DEKA (right) proteins. (G) FEP calculations for evaluating Na+/K+ selectivity at four positions defined in (B)
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