Table 2. Average RMSD, RMSF and total IE values, with standard deviations, derived from three MD simulation replicas of the complex between the NOP receptor and N/OFQ(1–13)-NH₂, RBM01, RBM03, MBM04 and MBM05. The trajectories were aligned on the receptors Cα atoms using the first frame as a reference. Each receptor and N/OFQ(1–13)-NH₂, RMSD and RMSF values were calculated only for Cα atoms, whereas for the small molecule ligands, all heavy atoms were considered. Values of the lowest RMSD, RMSF and IE detected among the three runs for each considered component of the trajectory (ligand and receptor) are in bold.

		RMSD		RMSF		IE
		RMSD_Lig_Ave ± σ [Å]	RMSD_Rec_Ave ± σ [Å]	RMSF_Lig_Ave ± σ [Å]	RMSF_Rec_Ave ± σ [Å]	Tot_Ave ± σ [kcal mol−1]
N/OFQ(1–13)-NH2	Run1	1.63 ± 0.30	1.23 ± 0.10	1.08 ± 0.27	0.76 ± 0.11	−628.55 ± 64.36
	Run2	1.69 ± 0.42	1.68 ± 0.18	1.08 ± 0.32	0.92 ± 0.16	−634.67 ± 72.47
	Run3	1.24 ± 0.28	1.29 ± 0.15	0.81 ± 0.31	0.78 ± 0.12	−653.04 ± 42.98
RBM01	Run1	2.74 ± 0.38	1.68 ± 0.17	0.86 ± 0.48	1.09 ± 0.19	−106.34 ± 9.20
	Run2	2.64 ± 0.25	1.61 ± 0.16	0.77 ± 0.34	1.02 ± 0.17	−125.01 ± 8.83
	Run3	1.29 ± 0.61	1.64 ± 0.16	1.06 ± 0.37	1.04 ± 0.14	−123.13 ± 9.78
RBM03	Run1	1.04 ± 0.27	1.46 ± 0.15	0.71 ± 0.19	1.26 ± 0.23	−118.88 ± 6.86
	Run2	1.44 ± 0.24	1.36 ± 0.13	0.60 ± 0.22	0.93 ± 0.15	−119.71 ± 7.09
	Run3	0.86 ± 0.20	1.82 ± 0.44	0.65 ± 0.19	1.12 ± 0.19	−116.97 ± 8.09
MBM04	Run1	2.95 ± 0.26	1.71 ± 0.17	1.12 ± 0.38	1.36 ± 0.19	−217.90 ± 40.68
	Run2	1.81 ± 0.42	1.52 ± 0.20	0.83 ± 0.43	1.46 ± 0.15	−243.07 ± 43.47
	Run3	2.41 ± 0.37	1.70 ± 0.16	1.04 ± 0.34	1.51 ± 0.17	−230.00 ± 43.83
MBM05	Run1	0.87 ± 0.20	1.79 ± 0.17	0.61 ± 0.14	1.41 ± 0.17	−273.31 ± 32.79
	Run2	1.04 ± 0.20	1.52 ± 0.25	0.66 ± 0.21	1.41 ± 0.18	−285.38 ± 19.86
	Run3	1.32 ± 0.20	1.49 ± 0.18	0.63 ± 0.18	1.34 ± 0.14	−249.32 ± 26.02