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Energetics of Ion Permeation in an Open-Activated TRPV1 Channel

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)1214-1222
Number of pages9
JournalBiophysical Journal
Issue number6
Early online date20 Sep 2016
Accepted/In press15 Aug 2016
E-pub ahead of print20 Sep 2016
Published20 Sep 2016


King's Authors


Ion channels enable diffusion of ions down physiological electrochemical gradients. Modulation of ion permeation is crucial for the physiological functioning of cells, and misregulation of ion channels is linked to a myriad of channelopathies. The ion permeation mechanism in the transient receptor potential (TRP) ion channel family is currently not understood at an atomistic level. In this work, we employed a simulation strategy for ion permeation (molecular-dynamics simulations with bias-exchange metadynamics) to study and compare monovalent (Na+, K+) ion permeation in the open-activated TRP vanniloid-1 (TRPV1) ion channel. Using ∼3.6 μs of simulation trajectories, we obtained atomistic evidence for the nonselective nature of TRPV1. Our analysis shows that solvated monovalent ions permeate through the selectivity filter with comparable energetic barriers via a two-site mechanism. Finally, we confirmed that an intracellular binding site is located between the intracellular gate residues I679 and E684.

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