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

ABSTRACT: The influenza A virus M2 channel (AM2) is crucial in the viral life cycle. Despite many previous experimental and computational studies, the mechanism of the activating process in which proton permeation acidifies the virion to release the viral RNA and core proteins is not well understood. Herein the AM2 proton permeation process has been systematically characterized using multiscale computer simulations, including quantum, classical, and reactive molecular dynamics methods. We report, to our knowledge, the first complete free-energy profiles for proton transport through the entire AM2 transmembrane domain at various pH values, including explicit treatment of excess proton charge delocalization and shuttling through the His37 tetrad. The free-energy profiles reveal that the excess proton

SUBMITTER: Liang R 

PROVIDER: S-EPMC4084430 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature