Table 1.

Main features of the all-atom molecular dynamics production simulations of the different CYPs

CYP	PDB ID	Environmentb	Ligandc	Ensembled	Time (ns)
CYP51 (T. brucei)	3G1Q	SOL	------	NPT	30
	3G1Q	MEM	------	NPγT	60
	3P99e	SOL	MCP	NPT	30
	3P99e	MEM	MCP	NPγT	15
CYP51 (human)	3LD6	SOL	------	NPT	15
CYP2C9_M1 (human)a	1R9O	SOL	------	NPT	28.28
	1R9O	MEM	------	NPγT	18.75
	1R9O	SOL	FLO	NPT	27.84
	1R9O	MEM	FLO	NPγT	11.25
CYP2C9_M2 (human)a	1R9O	SOL	------	NPT	27.78
	1R9O	MEM	------	NPγT	18.75
	1R9O	SOL	FLO	NPT	27.4
	1R9O	MEM	FLO	NPγT	11.25
CYP2E1 (human)	3KOH	SOL	------	NPT	10
	3T3Z	SOL	------	NPT	10

^aThe F-G loop region in the crystal structure of human CYP2C9 (PDB id: 1R9O) is missing. Two models of the F-G loop were generated for the simulations (Cojocaru et al., 2011). Model 1 has F′ and G′ helices, and model 2 has an unstructured F-G loop.

^bSOL, the soluble CYPs (no membrane); MEM, the membrane-bound CYPs in a lipid bilayer.

^cThe ligands used in the simulation. FLO, 4′-hydroxy flurbiprofen; MCP, 14α-methylenecyclopropyl-Δ7-24,25-dihydrolanosterol; “----”, ligand-free structures.

^dIn the NPγT simulations of the membrane-bound CYPs, a surface tension, γ = 60 dyn/cm, was applied to the plane of the membrane together with the pressure control to maintain the bilayer dynamics (Cojocaru et al., 2011). A comparison of the area per lipid, the bilayer thickness, and the order parameters of the membrane in the 60-ns simulation of the membrane-bound CYP51 with experimental data is plotted in Figures S6 and S7.

^eOnly the ligand MCP of 3P99 was transferred into the active site of the equilibrated ligand-free CYP51 structure (originally derived from the crystal structure 3G1Q). The simulations were then performed starting with this structure (see Methods).