Fig. 5: The upward movement of the F–F′ loop is critical for DHB exit.
From: Molecular dynamics simulations elucidate the role of the F–F′ loop in substrate entry into CYP3A4
DHB exit pathways through different tunnels in trajectories 0-1-3 (a) and 0-2-4 (d). The green F–F′ loops indicate loop movement in the absence of applied force, and the color gradient from red to blue illustrates the time-dependent positional change of DHB. Free energy profiles for DHB exit from the active site of CYP3A4 via tunnels in trajectory 0-1-3 (b) and 0-2-4 (e). Each panel presents two profiles: the red curve corresponds to simulations with a harmonic restraint applied to the backbone atoms of the F–F′ loop, while the black curve represents simulations conducted without the applied force. c, f Structures at the dashed points in (b, e). Left: Structure with applied force. Right: Structure without applied force. DHB is shown in pink, and the side chains of key residues are depicted in cyan using a licorice representation.
