Table 2. Standard Dissociation Free Energy Estimates (in kcal/mol) for the 21 Ligands Shown in Figure 2^b.

ligand	ΔGJ0	ΔGEM0	ΔGvol	ADconv	ADu	ADb	ΔGq	ΔGexp.
pari	10.7 ± 0.6	8.1 ± 4.1	–2.4	490.8	0.40	0.37	–8.6 ± 0.9	n/a
opa	9.4 ± 0.5	6.5 ± 3.1	–2.5	315.0	0.18	1.14	0.3 ± 0.8	n/a
ml	9.0 ± 0.7	9.0 ± 1.9	–3.2	131.1	0.15	0.45	–0.4 ± 0.6	7.9a
op3	8.8 ± 0.8	6.9 ± 1.8	–2.2	79.5	0.11	0.48	–2.5 ± 0.8	n/a
27	8.3 ± 0.5	8.1 ± 0.9	–2.7	165.6	0.40	0.54	–1.3 ± 0.3	n/a
39	7.6 ± 1.5	6.2 ± 2.8	–2.5	559.5	0.40	1.39	–1.8 ± 0.4	n/a
mma	7.4 ± 0.8	6.8 ± 1.7	–3.4	55.6	0.37	0.36	0.2 ± 0.4	n/a
ppa	7.3 ± 0.8	4.7 ± 2.5	–3.7	278.2	0.16	0.99	–3.6 ± 2.4	n/a
op2	7.1 ± 2.0	6.3 ± 3.1	–2.6	776.2	0.39	2.03	0.2 ± 0.6	n/a
dolu	6.7 ± 1.6	5.0 ± 3.4	–3.9	190.7	0.74	0.51	0.3 ± 2.0	n/a
19	6.5 ± 0.7	5.2 ± 1.5	–1.9	138.5	0.26	0.54	–3.2 ± 0.6	n/a
30	6.1 ± 0.9	5.1 ± 1.4	–3.5	116.7	0.38	0.43	–1.1 ± 0.3	n/a
mp2	5.8 ± 0.6	3.2 ± 1.4	–3.4	40.7	0.82	0.36	1.8 ± 1.2	n/a
mpa	4.3 ± 1.2	3.6 ± 2.9	–3.7	113.4	0.77	0.49	–1.5 ± 0.4	n/a
77	4.0 ± 0.4	2.3 ± 1.7	–3.0	141.7	0.17	0.53	–0.8 ± 2.4	n/a
n27	3.9 ± 0.6	2.9 ± 1.3	–2.5	114.0	0.42	0.46	–1.1 ± 0.4	n/a
79	3.7 ± 0.9	2.4 ± 0.9	–2.8	142.6	1.91	0.54	–0.4 ± 0.8	n/a
nml	3.1 ± 0.4	1.5 ± 0.5	–3.1	52.5	0.68	0.58	1.0 ± 0.9	n/a
1d45	5.4 ± 0.8	4.6 ± 1.1	–2.9	223.8	0.65	0.22	1.0 ± 0.9	10.0
0b12	9.3 ± 0.9	7.0 ± 1.6	–3.1	183.8	0.50	0.31	1.0 ± 0.9	7.46
2913	5.8 ± 0.8	5.5 ± 1.6	–2.8	201.5	0.63	0.52	1.0 ± 0.9	7.0

^aThe experimental value refers to the SARS-CoV 3CL^pro inhibition.¹⁵

^bΔG_J, Δ_EM, ΔG_vol, AD_conv, AD_u, AD_b, and ΔG_q refer to the Jarzynski free energy estimate; the EM-based free energy estimate; the volume correction; the AD normality test for P(W|F), P_u(−W|G), and P_b(W|A); and the electrostatic contribution to the dissociation free energy.