A Comprehensive Analysis of the TRPV1 Ion Channel via Coarse-Grained and Atomistic Simulations

The transient receptor potential (TRP) ion channels represent a significant class of proteins involved in physiological processes, particularly in thermosensation and pain perception. Among these, the transient receptor potential vanilloid 1 (TRPV1) channel—the most eminent member of the vanilloid subfamily—has been extensively studied as a therapeutic target fo neuropathic pain. TRPV1 is a tetrameric, ligand-gated, non-selective cation channel with activation mechanisms of noxious heat, acidic pH, and the vanilloid compound capsaicin. It is also notable for its low ionic selectivity, permitting the permeation of sodium and potassium, among other cations.

In my work, I investigated the structural and dynamical behavior of TRPV1 under varying temperature and salinity conditions using both atomistic molecular dynamics simulations and coarse-grained simulations based on the Martini 3 force field. My analyses focus on conformational modulation, inter-residue interaction networks, and lipid–protein coupling mechanisms relevant to channel conformation and gating. The lipid bilayers used in this study were designed to capture biologically relevant membrane heterogeneity beyond single-species systems. Finally, a proposed generalizable multiscale simulation framework was created that could be extended to the study of other ion channels within the TRP family and beyond.