Fig. 3
Modeling of the capsaicin-induced fully open state. a The models after six rounds of KIC loop modeling exhibited a funnel-shaped distribution of total energy calculated by Rosetta (R.E.U., Rosetta energy unit). b Top five models after the sixth round of loop modeling were well converged. The model with the lowest energy (red) was chosen as the open-state model. c Correlation between shifts in ANAP emission peak (y axis) and changes in SASA measured from our open-state model (x axis); n = 5–7. d Distribution of pore radii in the cryo-EM-derived closed state (3J5P) and our open-state model. In our model, both the selectivity filer region and the S6 bundle crossing are wide enough to allow permission of water molecules and ions. e Conductance of TRPV1 in different states predicted by the HOLE program. Our open-state model was predicted to have similar conductance as values measured by patch-clamp recording with 10 µM capsaicin17 (the bar in blue). The DkTx and RTX bound state structure (3J5R) determined by cryo-EM represented a fully open state, which shows a predicted conductance close to that of our open-state model and experimentally measured values. The predicted conductance of either the closed state (3J5P) or capsaicin bound state (3J5R) was much smaller (bars in gray). Data points are shown as circles. All statistical data are given as mean ± s.e.m
