Table 1.

Nearest neighbor free energy parameters derived experimentally compared to predicted values in this work (ΔG°_{37, predicted}) and from the RECCES-Rosetta framework (ΔG°_{37, Rosetta}) with average differences from A–U and G–C NN ΔG°₃₇ and RMSDs from experimental values. ΔG°_{37,experimental} refers to experimentally derived NN ΔG°₃₇ parameters for Watson–Crick, inosine·cytidine, isoguanosine·isocytidine, 2,6-diaminopurineriboside·uridine, and inosine·uridine obtained from references (19), (24), (25), (26) and (23), respectively. All values are reported in kcal/mol.

	NN	ΔG°37,experimental	ΔG°37,predicted	ΔG°37,Rosetta
Watson–Crick	AA	−0.93 ± 0.03	−1.02 ± 0.12	−1.13 ± 0.17
	UU
	AU	−1.10 ± 0.08	−1.11 ± 0.13	−0.91 ± 0.21
	UA
	UA	−1.33 ± 0.09	−1.34 ± 0.09	−1.26 ± 0.20
	AU
	AG	−2.08 ± 0.06	−2.16 ± 0.08	−2.19 ± 0.11
	UC
	CA	−2.11 ± 0.07	−2.19 ± 0.04	−2.09 ± 0.10
	GU
	AC	−2.24 ± 0.06	−2.03 ± 0.07	−1.95 ± 0.14
	UG
	GA	−2.35 ± 0.06	−2.18 ± 0.07	−2.13 ± 0.09
	CU
	CG	−2.36 ± 0.09	−3.02 ± 0.13	−2.89 ± 0.21
	GC
	CC	−3.26 ± 0.07	−3.21 ± 0.11	−3.29 ± 0.21
	GG
	GC	−3.42 ± 0.08	−3.09 ± 0.11	−2.88 ± 0.17
	CG
	RMSD		0.25	0.28
	MSE		−0.02	0.05
Inosine·cytidine	AI	−1.57 ± 0.44	−1.32 ± 0.11	−1.09 ± 0.14
	UC
	CI	−1.86 ± 0.31	−2.07 ± 0.32	−1.98 ± 0.20
	GC
	GI	−2.62 ± 0.40	−2.31 ± 0.09	−2.07 ± 0.26
	CC
	UI	−0.96 ± 0.40	−1.31 ± 0.14	−0.98 ± 0.25
	AC
	IA	−1.18 ± 0.44	−1.25 ± 0.07	−1.06 ± 0.11
	CU
	IC	−1.89 ± 0.31	−2.03 ± 0.21	−1.96 ± 0.13
	CG
	IG	−2.23 ± 0.40	−2.19 ± 0.22	−2.24 ± 0.16
	CC
	IU	−1.02 ± 0.40	−1.02 ± 0.13	−0.95 ± 0.21
	CA
	RMSD		0.21	0.27
	MSE		−0.02	0.13
	ΔA-U	−0.03	−0.05	0.09
	ΔG-C	0.97	0.95	1.09
Isoguanosine·isocytidine	AiG	N/A	−2.45 ± 0.26	−2.34 ± 0.26
	UiC
	CiG	−2.46 ± 0.08	−3.11 ± 0.23	−3.01 ± 0.39
	GiC
	GiG	−3.07 ± 0.11	−3.43 ± 0.31	−3.48 ± 0.22
	CiC
	UiG	N/A	−2.58 ± 0.27	−1.93 ± 0.24
	AiC
	iGA	N/A	−2.66 ± 0.04	−2.14 ± 0.23
	iCU
	iGC	−4.00 ± 0.09	−3.31 ± 0.27	−2.78 ± 0.18
	iCG
	iGG	−3.46 ± 0.11	−3.68 ± 0.09	−3.23 ± 0.16
	iCC
	iGU	N/A	−2.53 ± 0.26	−1.84 ± 0.27
	iCA
	RMSD		0.52	0.71
	MSE		−0.14	0.12
	ΔG–C	−0.22a	−0.33	0.04
2,6-Diaminopurine·uridine	AD	N/A	−1.42 ± 0.15	−2.32 ± 0.17
	UU
	CD	−2.72 ± 0.20	−2.24 ± 0.11	−3.57 ± 0.21
	GU
	GD	−3.10 ± 0.21	−2.37 ± 0.09	−3.10 ± 0.17
	CU
	UD	N/A	−1.78 ± 0.71	−2.61 ± 0.18
	AU
	DA	N/A	−1.45 ± 0.08	−2.28 ± 0.16
	UU
	DC	−2.62 ± 0.14	−2.35 ± 0.13	−2.80 ± 0.15
	UG
	DG	−2.28 ± 0.22	−2.33 ± 0.04	−3.20 ± 0.13
	UC
	DU	N/A	−1.41 ± 0.08	−1.85 ± 0.19
	UA
	RMSD		0.46	0.63
	MSE		0.36	−0.49
	ΔA–U	−0.49	−0.29	−1.08
	ΔG–C	0.40	0.71	−0.08
	Overall RMSDb		0.33	0.44
	Overall MSEb		0.02	0.00
Inosine·uridine	AI	−0.41 ± 0.47	−0.37 ± 0.17	N/A
	UU
	CI	−0.77 ± 0.39	−0.87 ± 0.14	N/A
	GU
	GI	−1.34 ± 0.33	−1.20 ± 0.34	N/A
	CU
	UI	0.37 ± 0.39	−0.13 ± 0.28	N/A
	AU
	IA	0.43 ± 0.43	−0.04 ± 0.35	N/A
	UU
	IC	−1.03 ± 0.30	−1.17 ± 0.16	N/A
	UG
	IG	−1.22 ± 0.37	−1.32 ± 0.23	N/A
	UC
	IU	−0.50 ± 0.44	−0.36 ± 0.06	N/A
	UA
	RMSD		0.26	N/A
	MSE		−0.12	N/A
	Overall RMSDc		0.32	N/A
	Overall MSEc		–0.01	N/A

^aValue estimated by halving the reported average duplex ΔG–C from (7).

^bOverall root mean square deviation (RMSD) and mean signed error (MSE) are for only WC, I·C, iG·iC, and DAP·U for direct comparisons to RECCES-Rosetta predictions.

^cOverall RMSD and MSE include WC, I·C, iG·iC, DAP·U and I·U data.