Subsequently, the biological relevance of the information contained in the 3DDPDs was investigated. One-hot encoding rs3DDPDs are calculated independently for each target and ps3DDPDs together for the targets in a particular set. Respectively, they exploit differences in atom coordinates and partial charges across positions in a target or a number of targets, representing the most relevant aspects of the protein dynamics, as defined by the RMSF fluctuations (Figure , Figures ). An advantage of rs3DDPDs is the possibility to be traced back to particular residues, alignment positions, or GPCR generic positions. This allowed us to investigate whether the 3DDPDs capture biologically relevant information from the MD simulation. To this end, the most important rs3DDPD features in regression PCM models were extracted and mapped to their corresponding GPCR generic positions (Figure ). The most important feature in a temporal split corresponded to the BW position 3.32 in TM3. As an example, in AA1R this translated to Val 87, which lies within the orthosteric binding pocket and makes hydrophobic interactions with the endogenous ligand adenosine (PDB 7LD4 ). Other important rs3DDPD features were located in the ECL2 and ECL3, which as expected showed high flexibility in the MD simulations and are regions whose conformational changes are known to be relevant for ligand binding and activation .