Figure 4. Molecular dynamics simulations to calculate hydration of Y671.

Molecular dynamics (MD) simulations of TRPV1 channels in the open (a) and closed (b) states. The upper and lower panels correspond to the side and top views of the S6 helices bundle (white), respectively. The pore helices (ph) are shown in blue. Y671 residues are represented as yellow sticks. In the open state, four Y671 residues create a ring oriented parallel to the membrane plane (perpendicular to the pore principal axis); whereas in the closed state, three of these residues do not interact with each other and are oriented perpendicular to the membrane plane (parallel to the pore principal axis). (c) Hydration of the channel central pore. Panel c shows the time evolution of the density profile (of water oxygens) along the pore. Specifically, at each time frame, the water oxygen atoms number density (i.e. the number of particles per unit of length) is calculated as a function of z (the axis of the pore). This quantity is shown using a color scale. Note that the units are Å⁻¹ (the number density for a linear system has the dimensions of the inverse of a length). The left and right panels correspond to the closed and open states, respectively. The y-axis of the plot denotes the z-axis of the system (parallel to the channel central pore). The origin of the axis is set at the center of the pore domain transmembrane part. The Y671 residues are located at ~2.5 Å. Note that in the open state, the water density is often interrupted starting from ~280 ns, whereas in the closed state, this density is continuous. (d) Solvent-accessible surface area (SASA) of Y671. Black and red curves correspond, respectively, to SASA over time for the open (black) and closed (red) states as indicated. In the closed state, the Y671 SASA is approximately twice as large as that in the open state starting from ~300 ns. (e) The panels show zoomed view of the Y671 in the closed (left) and open (right) states. In the open state, Y671 establishes a hydrogen bond with the Y671 of the adjacent subunit; whereas in the closed state, this residue interacts with the backbone of F640 located at the pore helix. The backbone of the selectivity filter (SF) is shown using a stick representation.