Fig. 4: DHB binding process and F–F′ loop upward movement in trajectories 0-1-3 and 0-2-4.
From: Molecular dynamics simulations elucidate the role of the F–F′ loop in substrate entry into CYP3A4
Time evolution of the Fe–O06 distance and F–F′ loop RMSD in trajectories 0-1-3 (a) and 0-2-4 (b). Trajectory frames were aligned to the crystal structure prior to RMSD calculation. The F–F′ loop adopts a downward-oriented conformation in the wheat-colored region and transitions upward after the wheat-white boundary, maintaining an upward-oriented conformation thereafter. The DHB molecule remains on the surface of CYP3A4 before the purple region and becomes trapped in the active site within the purple region. Structural comparison between the wheat–white boundary state and the dashed-point state in trajectories 0-1-3 (c) and 0-2-4 (d). Wheat-colored F–F′ loops and DHB molecules correspond to the wheat–white boundary in (a, b), while green-colored F–F′ loops and DHB molecules represent the structures at the dashed points. Structural comparison between the dashed-point state and the white–purple boundary state in trajectory 0-1-3 (e) and trajectory 0-2-4 (f). Pink-colored F–F′ loops and DHB molecules correspond to the white–purple boundary in (a, b). The side chain of R212 is explicitly shown.
