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Phys Chem Chem Phys. 2019 Apr 10. doi: 10.1039/c9cp00612e. [Epub ahead of print]

What are the effects of the serine triad on proton conduction of an influenza B M2 channel? An investigation by molecular dynamics simulations.

Author information

1
Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, International Joint Research Laboratory of Nano-Micro Architecture Chemistry, Jilin University, Changchun 130023, People's Republic of China. zhengqc@jlu.edu.cn.
2
Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, International Joint Research Laboratory of Nano-Micro Architecture Chemistry, Jilin University, Changchun 130023, People's Republic of China. zhengqc@jlu.edu.cn and Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun 130023, People's Republic of China.

Abstract

The tetrameric influenza B M2 channel (BM2), an acid activated proton channel, is important in the influenza virus B lifecycle. A conserved HxxxW motif is responsible for proton conduction and channel gating. In this study, to explore the effects of the serine triad (S9, S12 and S16) on proton conduction, we performed classical molecular dynamics (CMD) simulations and adaptive steered molecular dynamics (ASMD) simulations at different protonation states of the H19 tetrad. The results of the pore radius and the C-terminal tilt angle show that the electrostatic repulsion induced by protonated H19 is the key driving force for opening the BM2 channel. The open states could be stabilized by the hydrogen bonds between S16 and protonated H19. The solvent accessible surface area and water density indicate that the polar hydrophilic environment provided by the serine triad facilitates the formation of a water wire, and then exhibits favourable effects on proton conduction. The mutant research verifies and supports these views. Our work clarifies the effects of the serine triad on proton conduction in the BM2 channel, which would help us deeply understand the proton conduction mechanism in BM2 and provides a new perspective for antiviral drug design against BM2.

PMID:
30968902
DOI:
10.1039/c9cp00612e

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