Selective gating of essential molecules across cellular membrane is one of salient machinery that contributes the homeostasis of living cells. Synthetic transmembrane channels have been designed that can mimic the functionalities of natural channel proteins. These molecule bear a wide variety of applications in biomolecular and medicinal sciences. Recently, the Kim group at IBS/Postech reported a novel porphyrin based covalent organic cage, that can serve as an anion selective channel across cellular membrane. We elucidate the underlying mechanisms of the selective transport based on a set of molecular dynamics (MD) simulations. Long-time MD simulations (>10 μs ) of the cages embedded in model membranes showed that the internal cavity of the cage undergoes dewetting spontaneously. Umbrella sampling MD simulations showed that the dry state is thermodynamic minimum, whereas the wet states are energetically uphill only by a few kcal/mol that constitute local minimums in energy. These findings suggested that the wet state can occur intermittently, that explain the bursty ion flow observed experimentally. Metadynamics MD simulations of monovalent anions (I– and Cl–) confirmed that the wet state allows facile transport of anions and the dry state blocks the permeation. Moreover, we showed that iodide interacts favorably with the alkyl chains attached to the cages, that explains the higher permeability of iodide over chloride. Lastly, we compared the hydration propensities of the metal-free and the Zn(II) bound cages, that suggests a viable strategy to control the wet-dewetting behavior of the cages.