Multiscale Simulation of an Influenza A M2 Channel Mutant Reveals Key Features of Its Markedly Different Proton Transport Behavior.

ABSTRACT: The influenza A M2 channel, a prototype for viroporins, is an acid-activated viroporin that conducts protons across the viral membrane, a critical step in the viral life cycle. Four central His37 residues control channel activation by binding subsequent protons from the viral exterior, which opens the Trp41 gate and allows proton flux to the interior. Asp44 is essential for maintaining the Trp41 gate in a closed state at high pH, resulting in asymmetric conduction. The prevalent D44N mutant disrupts this gate and opens the C-terminal end of the channel, resulting in increased conduction and a loss of this asymmetric conduction. Here, we use extensive Multiscale Reactive Molecular Dynamics (MS-RMD) and quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations with an expl

SUBMITTER: Watkins LC 

PROVIDER: S-EPMC8834648 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature