Molecular Dynamics Simulation of Proton Transport through the Influenza A Virus M2 Channel

TitleMolecular Dynamics Simulation of Proton Transport through the Influenza A Virus M2 Channel
Publication TypeJournal Article
Year of Publication2002
AuthorsSmondyrev, AM, Voth, GA
JournalBiophys J
KeywordsBiological Transport Biophysical Phenomena Biophysics Carbon/chemistry Computer Simulation Diffusion Dimyristoylphosphatidylcholine/chemistry Influenza A virus/*metabolism Ion Channel Gating Ion Channels/chemistry/physiology Lipid Bilayers/*chemistry Mode, Molecular Models, Statistical Protons Time Factors Viral Matrix Proteins/*chemistry/*physiology

The structural and dynamical properties of a solvated proton in the influenza A virus M2 channel are studied using a molecular dynamics (MD) simulation technique. The second-generation multi-state empirical valence bond (MS-EVB2) model was used to describe the interaction between the excess proton and the channel environment. Solvation structures of the excess proton and its mobility characteristics along the channel were determined. It was found that the excess proton is capable of crossing the channel gate formed by the ring of four histidine residues even though the gate was only partially open. Although the hydronium ion itself did not cross the channel gate by traditional diffusion, the excess proton was able to transport through the ring of histidine residues by hopping between two water molecules located at the opposite sides of the gate. Our data also indicate that the proton diffusion through the channel may be correlated with the changes in channel conformations. To validate this observation, a separate simulation of the proton in a "frozen" channel has been conducted, which showed that the proton mobility becomes inhibited.