How two molecules self-assemble and what accelerates their assembly. Collectively, the 72 pathways indicate that the self-assembly process of Octacid4 with xylene, dioxane, and naphthalene was (1) initiated by the guest interaction with the cavity portal exterior of the host to increase the collisions of the portal that led to the portal expansion for guest ingress, (2) accelerated by engaging populated conformations of host and guest for the exterior intermolecular interaction to increase the portal collision frequency, and (3) completed by the portal contraction caused by the guest docking inside the cavity to impede guest egress. This type of self-assembly is a process of stepwise conformational rearrangements of the two molecules-kinetically starting from the pre-assembly state (at which the guest interacts with the exterior of the host) to the assembly-and post-assembly states (at which the guest interacts partially and fully with the interior of the host, respectively)-to gradually increase the attraction between the two molecules along a repulsion-free path until the maximal attraction is reached. The kinetics of this process was governed primarily by the complementarity between the two molecules during the priming time (on the order of microseconds or longer) rather than the ingress time (on the order of picoseconds).