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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|Titolo:||Energetics of Ion Permeation in an Open-Activated TRPV1 Channel|
|Citazione:||Jorgensen, C., Furini, S., & Domene, C. (2016). Energetics of Ion Permeation in an Open-Activated TRPV1 Channel. BIOPHYSICAL JOURNAL, 111(6), 1214-1222.|
|Appare nelle tipologie:||1.1 Articolo in rivista|
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