ArticleBiophysical journal2018
Decrypting the Heat Activation Mechanism of TRPV1 Channel by Molecular Dynamics Simulation.
Article in Biophysical journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- Molecular dynamics simulation of thermal activation of human TRPV1.Molecular biology research communications · 2026Article
- Biological and Biologically Inspired Functional Nanostructures: Insights into Structural, Optical, Thermal, and Sensing Applications.Advanced materials (Deerfield Beach, Fla.) · 2025Review
- Rational tuning of temperature sensitivity of the TRPM8 channel.EMBO reports · 2025Article
- Molecular Dynamic Simulations Reveal the Activation Mechanisms of Oxidation-Induced TRPV1.International journal of molecular sciences · 2023Article
- Biomedical and Antioxidant Potentialities in Chilli: Perspectives and Way Forward.Molecules (Basel, Switzerland) · 2022Review
- Decoding the Effect of Hydrostatic Pressure on TRPV1 Lower-Gate Conformation by Molecular-Dynamics Simulation.International journal of molecular sciences · 2022Article
- Ratio of Hydrophobic-Hydrophilic and Positive-Negative Residues at Lipid-Water-Interface Influences Surface Expression and Channel Gating of TRPV1.The Journal of membrane biology · 2022Article
- Venom Peptide Toxins Targeting the Outer Pore Region of Transient Receptor Potential Vanilloid 1 in Pain: Implications for Analgesic Drug Development.International journal of molecular sciences · 2022Review
- Single pulse heating of a nanoparticle array for biological applications.Nanoscale advances · 2022Article
- Antioxidant, Anti-Obesity, Nutritional and Other Beneficial Effects of Different Chili Pepper: A Review.Molecules (Basel, Switzerland) · 2022Review
- Simulation and Machine Learning Methods for Ion-Channel Structure Determination, Mechanistic Studies and Drug Design.Frontiers in pharmacology · 2022Review
- Molecular dynamics: a powerful tool for studying the medicinal chemistry of ion channel modulators.RSC medicinal chemistry · 2021Review
- Evidence that the TRPV1 S1-S4 membrane domain contributes to thermosensing.Nature communications · 2020Article
- Evolutionary analyses reveal independent origins of gene repertoires and structural motifs associated to fast inactivation in calcium-selective TRPV channels.Scientific reports · 2020Article
- Structural mechanisms of transient receptor potential ion channels.The Journal of general physiology · 2020Review
- Cytoplasmic Inter-Subunit Interface Controls Use-Dependence of Thermal Activation of TRPV3 Channel.International journal of molecular sciences · 2019Article
- Structural and Evolutionary Insights Point to Allosteric Regulation of TRP Ion Channels.Accounts of chemical research · 2019Article
- Heat activation mechanism of TRPV1: New insights from molecular dynamics simulation.Temperature (Austin, Tex.) · 2019Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As a prototype cellular sensor, the TRPV1 cation channel undergoes a closed-to-open gating transition in response to various physical and chemical stimuli including noxious heat. Despite recent progress, the molecular mechanism of heat activation of TRPV1 gating remains enigmatic. Toward decrypting the structural basis of TRPV1 heat activation, we performed extensive molecular dynamics simulations (with cumulative simulation time of ∼11 μs) for the wild-type channel and a constitutively active double mutant at different temperatures (30, 60, and 72°C), starting from a high-resolution closed-channel structure of TRPV1 solved by cryo-electron microscopy. In the wild-type simulations, we observed heat-activated conformational changes (e.g., expansion or contraction) in various key domains of TRPV1 (e.g., the S2-S3 and S4-S5 linkers) to prime the channel for gating. These conformational changes involve a number of dynamic hydrogen-bond interactions that were validated with previous mutational studies. Next, our mutant simulations observed channel opening after a series of conformational changes that propagate from the channel periphery to the channel pore via key intermediate domains (including the S2-S3 and S4-S5 linkers). The gating transition is accompanied by a large increase in the protein-water electrostatic interaction energy, which supports the contribution of desolvation of polar/charged residues to the temperature-sensitive TRPV1 gating. Taken together, our molecular dynamics simulations and analyses offered, to our knowledge, new structural, dynamic, and energetic information to guide future mutagenesis and functional studies of the TRPV1 channels and development of TRPV1-targeting drugs.
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