The open-close mechanism of M2 channel protein in influenza A virus: A computational study on the hydrogen bonds and cation-π interactions among His37 and Trp41

Abstract

The M2 protein from influenza A virus is a tetrameric ion channel. It was reported that the permeation of the ion channel is correlated with the hydrogen bond network among His37 residues and the cation-π interactions between His37 and Trp41. In the present study, the hydrogen bonding network of 4-methyl-imidazoles was built to mimic the hydrogen bonds between His37 residues, and the cation-π interactions between 4-methyl-imidazolium and indole systems were selected to represent the interactions between His37 and Trp41. Then, quantum chemistry calculations at the MP2/6-311G** level were carried out to explore the properties of the hydrogen bonds and the cation-π interactions. The calculation results indicate that the binding strength of the N-H…N hydrogen bond between imidazole rings is up to −6.22 kcal·mol−1, and the binding strength of the strongest cation-π interaction is up to −18.8 kcal·mol−1 (T-shaped interaction) or −12.3 kcal·mol−1 (parallel stacking interaction). Thus, the calculated binding energies indicate that it is possible to control the permeation of the M2 ion channel through the hydrogen bond network and the cation-π interactions by altering the pH values.