Table 1.

Comparison of calculated relative binding free energies of NTP and dNTP analogues to experimental values

Compound	ΔΔGMOE	ΔΔGFEPa	ΔΔGFEPb	−Δ(pKd)experimentalc	ErrorFEPb
	kcal/mol	kcal/mol	kcal/mol	kcal/mol	kcal/mol
3′-dATP	0.1	−1.6	−0.5	−0.5	0.0
7-Deaza-ATP	−7.6	1.3	−0.2	0.8	−2.0
2′-Deoxy-2′-fluoro-CTP	−4.4	−0.4	0.2	1.1	−0.9
2′-C-Methyl-CTP	−5.8	0.6	3.2	1.3	1.9
6-Methylpurine-TP	−19.3	0.3	1.2	1.6	−0.4
3-Deaza-ATP	−1.3	2.5	0.1	1.7	−1.6
2′-dATP	1.0	0.0	−0.2	1.8	−2.0
2′-C-Methyl-ATP	1.6	0.5	1.0	2.0	−1.0
4′-Methyl-CTP	−10.4	3.7	1.1	2.0	−0.9
2′-C-Methyl-GTP	7.9	1.1	2.8	2.5	0.3
Ribavirin-TP	11.9	2.5	3.7	3.0	0.7

^a Calculated under the condition of H1125 having a neutral charge state.

^b Calculated under the condition of H1125 having a +1 charge state.

^c Experimental results of Arnold et al. (3), except in the case of 2′-C-methyl-ATP; −Δ(pK_d)_experimental is taken from the average of the two values reported in Ref. 55.