In the models built with a random split, the two most important rs3DDPD features corresponded to TM1 1.38 and TM6 6.46 BW positions, respectively. In AA1R, these translated to Ile 15 and Leu 245, which flank the binding site of non-endogenous co-crystalized antagonists (PDB 5UEN ). The other two important rs3DDPD features correspond to positions in ICL3, which are close to the G protein interface (PDB 7LD3 ).