ArticleProceedings of the National Academy of Sciences of the United States of America2019
A heuristic derived from analysis of the ion channel structural proteome permits the rapid identification of hydrophobic gates.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 69 citations in OpenAlex.
- Non-Equilibrium Molecular Dynamics Simulation Captures Potential New Drug Target: Ec-MscL Gating Mechanism Explored with External Electric Field.Antibiotics (Basel, Switzerland) · 2026Article
- Lipid-mediated hydrophobic gating in the BK potassium channel.Nature communications · 2025Article
- Structural architecture of TolQ-TolR inner membrane protein complex from opportunistic pathogenScience advances · 2025Article
- Molecular mechanism of anion permeation through aquaporin 6.Biophysical journal · 2024Article
- Dynamic molecular portraits of ion-conducting pores characterize functional states of TRPV channels.Communications chemistry · 2024Article
- Structure-guided mutagenesis of OSCAs reveals differential activation to mechanical stimuli.eLife · 2024Article
- Structure-guided mutagenesis of OSCAs reveals differential activation to mechanical stimuli.bioRxiv : the preprint server for biology · 2024Article
- Mechanism of hydrophobic gating in the acetylcholine receptor channel pore.The Journal of general physiology · 2024Article
- Hydrophobic gating in bundle-crossing ion channels: a case study of TRPV4.Communications biology · 2023Article
- Atomic structure of the open SARS-CoV-2 E viroporin.Science advances · 2023Article
- Conformational trajectory of allosteric gating of the human cone photoreceptor cyclic nucleotide-gated channel.Nature communications · 2023Article
- Molecular Dynamic Simulations Reveal the Activation Mechanisms of Oxidation-Induced TRPV1.International journal of molecular sciences · 2023Article
- Central cavity dehydration as a gating mechanism of potassium channels.Nature communications · 2023Article
- Conformational transitions and allosteric modulation in a heteromeric glycine receptor.Nature communications · 2023Article
- Conserved patterns across ion channels correlate with variant pathogenicity and clinical phenotypes.Brain : a journal of neurology · 2023Article
- Structural Mechanism of Ionic Conductivity of the TRPV1 Channel.Doklady. Biochemistry and biophysics · 2023Article
- Molecular dynamics study of ClCellular and molecular life sciences : CMLS · 2023Article
- Targeting ion channels with ultra-large library screening for hit discovery.Frontiers in molecular neuroscience · 2023Review
- When is a hydrophobic gate not a hydrophobic gate?The Journal of general physiology · 2022Article
- Activation mechanism of the mouse cold-sensing TRPM8 channel by cooling agonist and PIPScience (New York, N.Y.) · 2022Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Ion channel proteins control ionic flux across biological membranes through conformational changes in their transmembrane pores. An exponentially increasing number of channel structures captured in different conformational states are now being determined; however, these newly resolved structures are commonly classified as either open or closed based solely on the physical dimensions of their pore, and it is now known that more accurate annotation of their conductive state requires additional assessment of the effect of pore hydrophobicity. A narrow hydrophobic gate region may disfavor liquid-phase water, leading to local dewetting, which will form an energetic barrier to water and ion permeation without steric occlusion of the pore. Here we quantify the combined influence of radius and hydrophobicity on pore dewetting by applying molecular dynamics simulations and machine learning to nearly 200 ion channel structures. This allows us to propose a simple simulation-free heuristic model that rapidly and accurately predicts the presence of hydrophobic gates. This not only enables the functional annotation of new channel structures as soon as they are determined, but also may facilitate the design of novel nanopores controlled by hydrophobic gates.
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