During the LSD-bound crystal structure, the side chain on the lid residue L209EL2 types extensive hydrophobic contacts with both of those LSD and bordering residues in TMs III, IV, and V (Figure 4C). Once the lid moved aside to expose the binding pocket in simulation, many of such contacts broke. https://jasperbkjhe.blazingblog.com/35086112/indicators-on-lsd-aztec-99-you-should-know