Demonstrating aspects of multiscale modeling by studying the permeation pathway of the human ZnT2 zinc transporter
Fig 2
Free energy calculations of zinc-binding along the putative YiiP and ZnT2 permeation pathways.
(A) Free energy of hydration for zinc in YiiP and ZnT2. The zinc-binding site (site A) is marked by a vertical line and the bulks are labeled. Each line represents the running average of several paths and starting structures (see methods), and the faded contour represents the SEM. The reaction coordinate is the distance (in Å) from the binding site, in the direction of the bulks. (B) The 2D energy landscape, using as coordinates the position of the zinc and the conformational change, the intermediate energies are computed as a linear interpolation of the IF and OF energies from (A) and the purpose is to provide a visual aid to the system’s energy landscape. (C) Model structures of ZnT2 exemplify the reaction coordinate for the zinc ion. In (A), (B) and (C), a pseudo random path depicting a zinc ion traversing the transporter is shown in dashed lines, split into 3 sections (see Exploration of the zinc permeation pathway in the Results and Discussion section).