Synthetic transmembrane channels that can mimic the functionalities of membrane protein counterparts possess a variety of applications in biomolecular and medicinal sciences. Recently, the Kim group at Postech/IBS demonstrated that a synthetic organic cage, covalently assembled from porphyrins and benzene triamines, behaves as an anion-selective channel, once embedded in lipid membranes. We investigated the underlying mechanisms of the ion permeation through the channel using molecular dynamics (MD) simulations as well as quantum mechanical calculations. Initially, we carried out a series of long time (&gt; 10 μs) MD simulations of the cage molecules within a model lipid bilayer. We discovered that the interior of the channel undergoes a complete dehydration spontaneously, that manifests the hydrophobic nature of the channel. Umbrella sampling MD simulations with a varying number of water molecules inside the channel showed that the dehydrated state is the thermodynamic minimum, whereas the hydrated states are metastable minima that are only a few kcal/mol higher in energy than the global minimum. The finding suggested that the hydration can occur intermittently. As the ion permeation through a dehydrated channel is energetically prohibitive, the intermittent hydration can explain the bursty ion conduction profiles observed experimentally. Indeed, additional MD simulations of monovalent anions (I- and Cl-) showed that the dehydrated channel is inaccessible for the anions, whereas the hydrated channel is permeable for the charged species. Finally, using a series of metadynamics MD simulations, we showed that iodide interacts more favorably with the alkyl chains that line the entrance of the channel, that explains the higher permeability of iodide over chloride observed. In short, the combined computational simulations explained the observed anion-selective ion-permeation through the synthetic channel and provided viable strategies to control the ion-transport behavior for specific applications.

Hydration-dehydration transitions and ion-carbon interactions control the selective anion transport through a synthetic cage embedded in lipid membrane

2019 Spring National Meeting

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