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.cation-π interaction, hydrogen bond, noncovalent interaction, ab initio calculation, M2 protein

Exploring Strong Interactions in Proteins with Quantum Chemistry and Examples of Their Applications in Drug Design

“…When it does break, the amantadine may come into the channel and form a cation-π bond with Trp-41. According to MP2/6–311+G(d,p) calculations, the cation-π interaction energy between amantadine and the Trp-41 is -78.70 kJ/mol [ 69 ] in the gaseous phase. However, in an aqueous solution, this cation-π interaction energy may decrease to -13.27 kJ/mol.…”

Theoretical study of the interaction mechanism of single-electron halogen bond complexes H3C⋯Br-Y (Y = H, CN, NC, CCH, C2H3)

“…Since the discovery of weak interactions, increasing attention has been paid to theoretical and experimental investigations of hydrogen bonds due to their very important roles in chemistry, physics and biology [1][2][3]. A number of unusual hydrogen bonds, including the dihydrogen bond [4], the π hydrogen bond [5], the anion hydrogen bond [6], the longrange π-type hydrogen bond [7], the monoelectron dihydrogen bond [8] and the electron-hydrogen bond [9] have been proposed and extensively studied.…”

Adamantan derivatives capable of inhibiting the reproduction of a Rimantadine resistant strain of influenza A(H1N1)pdm09 virus <i>(Influenza A virus, Alphainfluenzavirus, Orthomyxoviridae)</i>

“…Протоны, попавшие внутрь вириона, понижают pH внутренней среды, что приводит к диссоциации комплекса матриксного белка М1 с рибонуклеопротеином и, как следствие, к высвобождению вирусной РНК в цитоплазму клетки хозяина. Наиболее важную роль в транспорте протонов через канал М2 играют аминокислотные остатки гистидина (His37) и триптофана (Trp41) в ТМ-домене [3,4].…”

“…Как утверждают некоторые источники, ингибирующее действие молекул римантадина и амантадина тесно связано с необходимостью образования водородной связи между аминоадамантаном и гидроксильной группой остатка серина в 31-м положении на внутренней поверхности канала М2 [3]. Однако ряд исследований показывает, что данное взаимодействие необязательно для закрепления ингибитора в поре канала [6].…”