Exploring Histidine Conformations in the M2 Channel Lumen of the Influenza A Virus at Neutral pH via Molecular Simulations.

ABSTRACT: The pH-regulated M2 proton channel from the influenza A virus has a His-tetrad in its transmembrane (TM) domain that is essential for proton conduction. At neutral pH, the tetrad has been observed in two distinct configurations, the "His-box" and "dimer-of-dimers", with similar backbone structures suggesting competing models for proton conduction. Here, we propose that both conformations can play a role. In support of this hypothesis, we used molecular dynamics simulations based on density functional theory to simulate the M2-TM domain and force-field-based simulations to estimate the relevant free-energy barriers. Both configurations are stable on accessible simulation time scales, and transitions between them occur faster than the millisecond time scale of proton conduction. Moreover, th

SUBMITTER: Dong H 

PROVIDER: S-EPMC3779100 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature