Figure gives a high level overview of the GCNCMC protocol. In summary, the entire protocol involves running regular MD to propagate the system, with GCNCMC moves interspersed. An insertion or deletion move is selected with equal probability, and, for an insertion move, a non-interacting molecule is randomly placed into a user-defined GCMC region and 'switched on'. For a deletion move, a fully interacting molecule within the GCMC region is selected randomly and then 'switched off'. These switches are governed by a series of alchemical perturbations and a small amount of MD between each perturbation such that the entirety of the switch is performed out of equilibrium, or in other words, the simulation does not have time to equilibrate during the move. At the end of the GCNCMC move, a Monte Carlo acceptance test is performed and the move is either accepted or rejected based on the thermodynamic properties of the system including the excess chemical potential, and the desired concentration of the molecule being switched. Conceptually, higher concentrations would drive the acceptance of insertion moves and vice versa for deletion. If the move is accepted, the simulation continues from this state, and, if the move is rejected, the simulation restarts from the state prior to the attempted move.