Given the positive bias towards inactive conformations, apo simulations in inactive conformation were selected for class A GPCRs with available bioactivity data (see PCM bioactivity modelling). When more than one system was available PDB codes with true apo 574 structure with the highest resolution were selected (Table ). Most selected MD trajectories 575 had been simulated in triplicate for 500 ns over 2,500 frames following the GPCRmd 576 standardized pipeline. The exceptions were GPCRmd ID 87 with 1,250 frames and ID 154 577 with 2,000 frames. For the generation of 3DDPDs, the first replicate was selected for each 578 system. 579 Python library MDtraj was used to compute Root Mean Square Deviation (RMSD) and RMSF of MD trajectories to assess the stability of the simulations and account for differences in the dynamic behaviour of the selected GPCRs in different protein segments. RMSD was calculated for the protein atoms in reference to the first frame in the production run. RMSF was calculated for the protein Cα backbone atoms over the total length of the simulation. To allow direct comparison between receptors, RMSF values were aligned based on their corresponding residue number to the class A GPCR MSA obtained from GPCRdb . The location of TM domains in the RMSF plots was mapped based on the generic BW residue numbers obtained from GPCRdb. BW were also used through the manuscript to refer to equivalent locations in the GPCR structure.