Multiscale simulation reveals a multifaceted mechanism of proton permeation through the influenza A M2 proton channel

• DOI: 10.1073/pnas.1401997111
• Publication Date: 2014-06-17T02:56:38Z
• Authors: Ruibin Liang; Hui Li; Jessica M. J. Swa...; Gregory A. Voth
• Keywords: Models, Molecular; Viral Matrix Proteins; Influenza A virus; Hydrogen-Ion Concentration; Molecular Dynamics Simulation; Protons; 01 natural sciences; Virus Release; 3. Good health; 0104 chemical sciences

Significance The M2 channel in the influenza A virus is one of three commonly targeted proteins viral membrane. Proton permeation across acidifies virion, releasing RNA and core proteins. This work constitutes, to our knowledge, first complete characterization this process by multiscale computer simulation, results are quantitative agreement with prior experimental measurements. simulations confirm that mechanism involves a “shuttling” protons through His37 tetrad rate-limiting step histidine deprotonation. also reveal several important features, including large barrier for reach increased conductance lower pH values due broadening solvent dynamics despite larger charge repulsion.