In our experience, a benefit of the NEQ approach is that it can be easier to do sanity checks. Only two long simulations are performed in the physical states which is easier than having to check all trajectories along the alchemical path in EQ. The long end state simulations also provide a point of reference to check that the transition simulations are capturing the right motions. Specifically, an A → B transition needs to (at least some fraction of the time) end up at snapshots that are representative of the same B state seen in the long equilibrium B simulation. This could be done in a systematic and automated way by ensemble comparison techniques.