Fig. 2.

The distance between the COMs of the ligand and the binding site residues,$d_{\mathrm{COM}}$, of selected ligands during 20 ns MD simulations. The distance is shown for the detaching ligands conivaptan (CVT, orange), 2-hydroxyestrone (HES, red) and ZINC000008764269 (N11, dark red). The cutoff distance at 15 Å is indicated by a black line. The reference compound N3 (blue) does not detach despite transient motions away from the binding site. For comparison, the distances of the ligands displaying the smallest $d_{\mathrm{COM}}$ in each ligand class are shown (from dark to light green): indocyanine (IDC, FDA), UK-432,097 (UK4, INV), theacitrin A (TCA, NP) and 17-$\alpha$-hydroxypregnanolone (AHP, ST).