TABLE 2.

MD simulations performed in the present study

Systema	Binding mode in agreement with mutational datab	Rotamer changec	Receptor activationd	MD simulation
				Duration	Time for rotamer changee
				ns
HU210-CB1y1	No	Yes	No	60	∼17
HU210-CB1y2	Yes	Yes	No	56	∼11
HU210-CB1y3	Yes	Yes	Yes	60	Immediatef
CP55940-CB1y	Yes	Yes	Yes	59	∼15
Δ9-THC-CB1n	Yes	No	No	50
CB1n		No	No	36

^a All simulations were performed in a fully hydrated lipid-bilayer using POPC (see “Experimental Procedures”).

^b Judged by the interaction between the C3 alkyl chain and the ligand-contacting residues, Leu-193^3.29, Val-196^3.32, Leu-359^6.51, and Met-363^6.55.

^c Judged by the Trp-356^6.48 χ1 angle: if trans (i.e. +120° < χ1 < +240°) yes; otherwise, no.

^d Judged by the orientation of the Trp-356^6.48 side chain indole ring: if the indole ring faces toward H5 (91), yes; otherwise, no.

^e The time taken for the rotamer change as judged by the Trp-356^6.48 χ1 angle.

^f In this case, the initial structure included the Trp-356^6.48 rotamer change (see text).