Figure 2.

Most populated clusters of the drugs benzocaine and phenytoin obtained from 300 ns of molecular dynamics simulation where blue, red, yellow and cyan represent progressively less populated clusters. While the full pore forming domain of NavAb (residues 115–221) was used in these simulations, for clarity, only selected residues (200–221) from 3 of the 4 S6 helices are shown in this figure. A: In the 1S system benzocaine remained in the activation gate. B: In the 4S system benzocaine was not able to pass the bulky aromatic residues and remained in the vicinity of the fenestrations. The blue cluster is pi-stacking with F206. C: In the 1S system phenytoin was able to sit in the center of the cavity (red) and move and rotate in the vicinity of the fenestrations (blue, yellow and cyan clusters). D: In the 4S system phenytoin is more restricted in its movement and remains in a pocket formed by the aromatic residues and M209 (blue) or straddles F206 in the fenestration (red).