Fig. 4. Nalfurafine, U50,488, and WMS-X600 favor different receptor conformations.

a Side and intracellular views of representations of the occluded (blue) and alternative state (green) compared to the canonical state (gray). Here the alternative and occluded states are represented by simulation frames and the canonical state is represented by the KOR-nafurafine-Nb39 crystal structure. b Density plots of the distance between the carboxylate oxygens of D334^8.47 and the hydroxyl oxygen of T94^2.39 and the rotation of TM7 at the S324^7.47 (see “Methods”). Simulation frames were classified as being in the occluded state if the T94^2.39–D334^8.47 distance is less than 3.5 Å and otherwise in the alternative state if the TM7 rotation is less than −20° or else in the canonical active state.