Figure 2.

Structural elements correlated with the conformational changes along the first principal component vector (PC1). (A) The conformational transition observed in the MD1 simulation is represented as a superposition of 15 frames, selected equidistantly along the γ₁(t) of MD1, from the occluded (dark green) to the outward-open conformation (gray). The eigenvectors of PC1 of MD1 and MD2 are also visualized in Movie S1 and Movie S2, respectively. (B and C) Zoomed-in views of the region near the Na1 site in the most occluded (B) and most open (C) frames in panel A. Water molecules are represented as red beads. In panel C, nonbonded interactions between Asn-27 and Na⁺ are marked by dashed lines. (D) Distribution of the HAs and HDs that are correlated with the γ₁(t) of MD1. The top 40 HA or HD segment pairs that correlated directly (positive values, green) and inversely (negative values, orange) are mapped onto an outward-open LeuT model viewed from the extracellular side. The bars connect the centers of mass of the segment pairs; the radii of the spheres are drawn in proportion to the frequencies of the involved segments. The most frequently involved segments are EL3b and TM6a (green) and TM11 (orange). (E and F) Distributions of 40 HAs and HDs that are most correlated with the Na1 and Na2 binding enthalpies, respectively. The viewing angle, representation, and color schemes are the same as panel A. No HA or HD that is correlated with the Na2 enthalpy involves TM10a (dotted circle in F). This is a distinct difference from the correlation patterns observed for the Na1 enthalpy and γ₁(t). Correlation coefficients are given in Table S2.