Fig. 4: Specific interactions between menthol isopropyl legs and the channel probed with isopulegol.
From: Molecular mechanisms underlying menthol binding and activation of TRPM8 ion channel
a Chemical structures of menthol and isopulegol. The isopropyl group in menthol is replaced by the methylethenyl group in isopulegol (dashed box in red). b The concentration–response curves of wild type and mutant such as I846V with either menthol or isopulegol were measured with whole-cell patch-clamp recordings (n = 3–5). c, d For wild type and I846V channel, Kd and L values were calculated from the concentration–response curves in c (two-sided t-test, *p < 0.05; NS not statistically significant). e Summary of coupling energy measurements. Coupling energy value was calculated from the Kd values. Mutants showing a coupling energy larger than 1.5 kT (dashed line) were colored in red. Those with less energy were colored in different shades of blue. At least four independent trials were performed for each chemical at each concentration. f Spatial distribution of coupling energy values within the menthol-binding pocket. Color scheme is the same as in e. Color scale is in the unit of kT. g Structural fluctuation in the menthol-bound S1–S4 domain during 378 ns molecular dynamic simulation. Root-mean-square deviation (RMSD) of protein structures was calculated as compared to our menthol docking model. h Ensemble plot of the menthol molecule (dashed box in yellow) with snapshots of the simulation from the beginning to the end (red and blue, respectively). A snapshot was saved every 10 ns during the simulation. All statistical data are given as mean ± s.e.m. Source data are provided as a Source Data file.
