ArticleThe journal of physical chemistry letters2013
Exploring Histidine Conformations in the M2 Channel Lumen of the Influenza A Virus at Neutral pH via Molecular Simulations.
Article in The journal of physical chemistry letters, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- The interplay of polarizable water and protein in the activation of the M2 channel.Frontiers in pharmacology · 2025Article
- From Acid Activation Mechanisms of Proton Conduction to Design of Inhibitors of the M2 Proton Channel of Influenza A Virus.Frontiers in molecular biosciences · 2021Review
- Acid activation mechanism of the influenza A M2 proton channel.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Viral channel forming proteins--How to assemble and depolarize lipid membranes in silico.Biochimica et biophysica acta · 2016Review
- High-resolution structures of the M2 channel from influenza A virus reveal dynamic pathways for proton stabilization and transduction.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Molecular dynamics, monte carlo simulations, and langevin dynamics: a computational review.BioMed research international · 2015Review
- Proton release from the histidine-tetrad in the M2 channel of the influenza A virus.The journal of physical chemistry. B · 2014Article
- Multiscale simulation reveals a multifaceted mechanism of proton permeation through the influenza A M2 proton channel.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Mechanistic insights from functional characterization of an unnatural His37 mutant of the influenza A/M2 protein.Biochimica et biophysica acta · 2014Article
- Theoretical frameworks for multiscale modeling and simulation.Current opinion in structural biology · 2014Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
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, the deprotonation energy is too high for spontaneous conduction, consistent with their occurrence in the low-current regime. Our computations support a multiconfiguration model with different population levels, thereby connecting experimental data obtained under different conditions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.