ArticleScientific reports2020
Insights on small molecule binding to the Hv1 proton channel from free energy calculations with molecular dynamics simulations.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Modulators of the Human Voltage-Gated Proton Channel HPharmaceuticals (Basel, Switzerland) · 2025Review
- Quantitative insights into the mechanism of proton conduction and selectivity for the human voltage-gated proton channel Hv1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Alchemical Free Energy Calculations on Membrane-Associated Proteins.Journal of chemical theory and computation · 2023Review
- Correction Schemes for Absolute Binding Free Energies Involving Lipid Bilayers.Journal of chemical theory and computation · 2022Article
- Gating Mechanism of the Voltage-Gated Proton Channel Studied by Molecular Dynamics Simulations.Molecules (Basel, Switzerland) · 2022Article
- Molecular dynamics: a powerful tool for studying the medicinal chemistry of ion channel modulators.RSC medicinal chemistry · 2021Review
- HIFs: New arginine mimic inhibitors of the Hv1 channel with improved VSD-ligand interactions.The Journal of general physiology · 2021Article
- Thermodynamics and Mechanism of the Membrane Permeation of Hv1 Channel Blockers.The Journal of membrane biology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Hv1 is a voltage-gated proton channel whose main function is to facilitate extrusion of protons from the cell. The development of effective channel blockers for Hv1 can lead to new therapeutics for the treatment of maladies related to Hv1 dysfunction. Although the mechanism of proton permeation in Hv1 remains to be elucidated, a series of small molecules have been discovered to inhibit Hv1. Here, we computed relative binding free energies of a prototypical Hv1 blocker on a model of human Hv1 in an open state. We used alchemical free energy perturbation techniques based on atomistic molecular dynamics simulations. The results support our proposed open state model and shed light on the preferred tautomeric state of the channel blocker. This work lays the groundwork for future studies on adapting the blocker molecule for more effective inhibition of Hv1.
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Registered trials
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