ArticleBiophysical journal2016
Multiscale Simulations Reveal Key Aspects of the Proton Transport Mechanism in the ClC-ec1 Antiporter.
Article in Biophysical journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 69 citations in OpenAlex.
- Hydration-Controlled Proton Transport in Respiratory Complex I.Journal of the American Chemical Society · 2026Article
- Molecular mechanism of exchange coupling in CLC chloride/proton antiporters.Nature communications · 2026Article
- Molecular simulations meet personalized medicine: The mechanism of action of CLC-5 antiporter and the origin of Dent's disease.PNAS nexus · 2025Article
- Ion Channel Reaction Networks: Dielectric Screening and the Importance of Off-Pathway Flux.Journal of chemical theory and computation · 2025Article
- Multiscale Responsive Kinetic Modeling: Quantifying Biomolecular Reaction Flux under Varying Electrochemical Conditions.Journal of chemical theory and computation · 2025Article
- Nernst equilibrium, rectification, and saturation: Insights into ion channel behavior.Biophysical journal · 2024Article
- Multiscale Responsive Kinetic Modeling: Quantifying Biomolecular Reaction Flux under Varying Electrochemical Conditions.bioRxiv : the preprint server for biology · 2024Article
- Molecular Dynamics Simulation of Complex Reactivity with the Rapid Approach for Proton Transport and Other Reactions (RAPTOR) Software Package.The journal of physical chemistry. B · 2024Article
- Structural basis of pH-dependent activation in a CLC transporter.Nature structural & molecular biology · 2024Article
- Fluoride Transport and Inhibition Across CLC Transporters.Handbook of experimental pharmacology · 2024Article
- The role of conformational change and key glutamic acid residues in the ClC-ec1 antiporter.Biophysical journal · 2023Article
- Generalized Transition State Theory Treatment of Water-Assisted Proton Transport Processes in Proteins.The journal of physical chemistry. B · 2022Article
- Multiscale kinetic analysis of proteins.Current opinion in structural biology · 2022Review
- Multiscale Simulation of an Influenza A M2 Channel Mutant Reveals Key Features of Its Markedly Different Proton Transport Behavior.Journal of the American Chemical Society · 2022Article
- A quantitative paradigm for water-assisted proton transport through proteins and other confined spaces.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Improved Indicator Algorithms for Tracking a Hydrated Proton as A Local Structural Defect in Grotthuss Diffusion in Aqueous Solutions.Chemical physics letters · 2021Article
- Accurate and Transferable Reactive Molecular Dynamics Models from Constrained Density Functional Theory.The journal of physical chemistry. B · 2021Article
- Toward a Multipathway Perspective: pH-Dependent Kinetic Selection of Competing Pathways and the Role of the Internal Glutamate in ClThe journal of physical chemistry. B · 2021Article
- Article
- Influenza A M2 Inhibitor Binding Understood through Mechanisms of Excess Proton Stabilization and Channel Dynamics.Journal of the American Chemical Society · 2020Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Multiscale reactive molecular dynamics simulations are used to study proton transport through the central region of ClC-ec1, a widely studied ClC transporter that enables the stoichiometric exchange of 2 Cl(-) ions for 1 proton (H(+)). It has long been known that both Cl(-) and proton transport occur through partially congruent pathways, and that their exchange is strictly coupled. However, the nature of this coupling and the mechanism of antiporting remain topics of debate. Here multiscale simulations have been used to characterize proton transport between E203 (Glu(in)) and E148 (Glu(ex)), the internal and external intermediate proton binding sites, respectively. Free energy profiles are presented, explicitly accounting for the binding of Cl(-) along the central pathway, the dynamically coupled hydration changes of the central region, and conformational changes of Glu(in) and Glu(ex). We find that proton transport between Glu(in) and Glu(ex) is possible in both the presence and absence of Cl(-) in the central binding site, although it is facilitated by the anion presence. These results support the notion that the requisite coupling between Cl(-) and proton transport occurs elsewhere (e.g., during proton uptake or release). In addition, proton transport is explored in the E203K mutant, which maintains proton permeation despite the substitution of a basic residue for Glu(in). This collection of calculations provides for the first time, to our knowledge, a detailed picture of the proton transport mechanism in the central region of ClC-ec1 at a molecular level.
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