to initiate MD simulations and (b) several hundred pairwise distances to monitor during MD. First, the structures are passed through an RMSD filter, which by default uses the structure with the highest pLDDT score as the reference to exclude unfolded or unrealistic structures. Additional user-defined filters can also be applied. Next, the user selects regions of the protein to compute pairwise distances. This is the stage where a priori knowledge about the system can be applied. In our case with ADK and DDR1, we focused on regions known to undergo conformational changes to prioritize the most relevant domains. The pairwise distance features are ranked by their coefficient of variance (CoV = variance/mean), and the top few hundred are selected. Finally, regular space clustering is applied to the selected subspace using a distance threshold to identify a few cluster centers.