Fig. 3: DHB resides on the surface of CYP3A4 for an extended period 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
In trajectory 0-1-3, DHB is stabilized at the entrance of the cyan tunnel (tunnel 2b) from 4.6 to 9.6 μs (a), while in trajectory 0-2-4, it is stabilized at the entrance of tunnel 2a (between helices A′ and F′) from 0 to 7 μs (d). The F–F′ loop is shown in green, and part of the B–C loop is colored magenta. Multiple colored F–F′ loops illustrate positional changes, and a color gradient traces the time-dependent positional change of DHB. Time evolution of the Fe–C26 and Fe–O06 distances, as well as the F–F′ loop RMSD, is shown for the 4.6–9.6 μs interval in trajectory 0-1-3 (b) and the 0–7 μs simulation in trajectory 0-2-4 (e). c Representative structure of bound DHB (pink), stabilized by nearby residues R106 and Q79, as well as by another DHB molecule (yellow) in trajectory 0-1-3. Hydrogen bonds are indicated. f Representative structure of bound DHB stabilized by residue Y53 in trajectory 0-2-4.
