(A) The bottom view and (B) the side view of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) molecules moving around H1423. The transient receptor potential (TRP) domain is shown in blue, the S4S5 linker is shown in cyan, and the POPC density around H1423 is shown with silver transparent surfaces. The analysis was performed on the molecular dynamics (MD) trajectory FI0. (C) The initial (salmon) and final (violet) locations of a POPC molecule in the MD simulation trajectory FI0. (D) A lipid molecule was observed in the cryo-EM structure of NompC (PDB ID: 5vkq). The pocket between H1423 and S1268 can stably accommodate a lipid molecule in both the MD simulations and the cryo-EM structure. (E) The representative traces of the spontaneous NompC current before/after adding OAG to the intracellular monolayer of the membrane, and the corresponding average open probabilities (N = 5, paired Student’s t-test, p=0.0208). (F) The representative traces of the spontaneous NompC current before/after adding OAG to the extracellular monolayer of the membrane, and the corresponding average open probabilities (N = 5, paired Student’s t-test, p=0.0047).