After path processing illustrated in the previous steps, we end up with waypoints optimally aligned on the protein structure where the ligand gradually moves from the bound pose to the solvated one. Ideally, we want to compare waypoints with the same index for the distance's compute cost to scale linearly with path length, however, this requires that all paths contain the same number of waypoints. While the waypoints are extracted to have a fixed spacing, the number of extracted waypoints may be uneven for all replicas (Figure ). To achieve consistent spacing and the same number of waypoints, we extend paths by translating the last waypoint using the displacement between it and the second to last waypoint until all paths have been extended to the maximum number of waypoints among all the paths (Figure ). These extrapolated waypoints are only used for comparison during clustering. Once all paths have the same spacing and number of waypoints we can calculate the distance D ij between paths as