Figure 8

Molecular modelling of ligand docking into the putative menthol binding site of the TRPM8 receptor. Parts of the S1-S4 domains of TRPM8 are depicted and residues Y745 in S2 and N799 and D802 in S3 are highlighted. A, Menthol makes a hydrogen bond with Y745 (S2), disrupting its interaction with D802 (S3). B, BCTC is located externally of Y745 preventing the interaction with this residue. C, SKF96365 interacts with Y745 and N799, stabilizing the positions of the S2 and S3 domains. The TRPM8 model was built using the coordinates of Pedretti et al. [38].