showed conformational distributions with dihedral angle 2 around +60° and +180°, but not with dihedral angle 2 in the range from 0° to -180°, because of the rotational restriction caused by changing glycerol to a tetrahydropyran ring (Figure ). In the case of the cis isomers, the histogram of cis-1a-2p displayed conformations with dihedral angle 1 around ±60°, but there are no low-energy conformations with dihedral angle 1 around ±120° to ±180° (Figure ). On the other hand, cis-1p-2a showed conformations with dihedral angle 2 around ±60°, while there were no conformations in the ranges from +120° to +180° and from -120° to -180° (Figure ). These REMD results are summarized in Table , where yellow highlighting indicates accessible conformations and a mark indicates possible bioactive ligand conformations. In the case of the bioactive compounds trans-1a-2p and cis-1a-2p, the accessible conformations will include the bioactive ligand conformation, whereas in the case of inactive trans-1p-2a and cis-1p-2a, the bioactive conformation would not overlap with the accessible regions. Table indicates the number of overlaps of the four cyclic LysoPS analogs with respect to the two dihedral angles (yellow, one; orange, two; pink, three; red, four), where "overlap" is defined to occur where the active analogs (trans-1a-2p and cis-1a-2p) sampled possible bioactive conformations (marked by '✔'), and where the inactive analogs (trans-1p-2a and cis-1p-2a) did not sample the bioactive conformations. The red boxes (+60 and -180) contain the active compounds, but do not contain the inactive compounds. Thus, these REMD results suggested that the dihedral angle range of around +60° (D1) and -180° (D2) may contain the bioactive ligand conformation for GPR34.