Computational modeling of scmtr: A synthetic anion channel.

摘要

SCMTR, Synthetic Chloride Membrane TRansporter, is a heptapeptide-based synthetic anion-selective channel-forming compound. Experimental work has demonstrated the efficacy of SCMTR as a channel-former. Unfortunately, experimental work has been unable to provide a full picture of the channel formation at an atomistic level. In this study, quantum mechanical calculations and molecular dynamic simulations were performed to expand our understanding of how SCMTR functions. Molecular dynamics simulations were performed to gain insight into the channel-forming capabilities of the SCMTR class of anion channels. These results support pore formation by the experimentally predicted single-surface dimeric SCMTR configuration. Simulated currents of 11.1 pA and 3.7 pA were reported for simulations involving a charge imbalance on either side of the bilayer and simulations where an electric field is applied, respectively. Stable water-channels were formed; these began from the SCMTR and extended to the opposing face. Removal of the driving force within the charge separation simulation was found to close the pore within a 10-ns simulation. As predicted, opposing face lipid head-group rearrangement was found to assist in the stabilization of the water-channel. Furthermore, these results suggest that the SCMTR molecules may help thin the bilayer by moving deeper into its surface and, thereby, helping to stabilize the water-channel. These results confirm that the proposed dimeric insertion model is sufficient to stabilize a channel, while providing atomistic insight into the channel's function. Using density functional theory, static and scanning optimizations were performed on glycine and proline containing oligomers to provide insight into the selectivity mechanism of the SCMTR molecule. These calculations established direct hydrogen bond dimensions of 2.358 and 3.359 A for interatomic distances between a chloride anion and the amide hydrogen and nitrogen, respectively. The average hydrogen bond angle was predicted to be 169.21 degrees. Furthermore, these calculations predict a hydrogen bond energy of approximately 1 to 3 kcal/mol, which is consistent with the channel-forming behavior.