In the models built with a random split, the two most important rs3DDPD features, AA128_PC2 and AA576_PC5, corresponded to TM1 1.38 and TM6 6.46 BW positions, respectively (Figure ). In AA1R, these translated to Ile 15 and Leu 245 (Figure ). The other two important rs3DDPD features correspond to positions in ICL3. Of note, the consensus between seeds on the importance of specific rs3DDPD features was less marked on the models with random split than the models with temporal split (Figure ). This analysis was further applied to discuss the relevance of specific GPCR positions in ligand binding.