Table 3.

Filtering by ligand stability during equilibration MD and FEP/MD calculations to predict ligand-binding mode^a

System	Cognate docking				Noncognate docking
	RMSDnat	docking score	RMSDMD	$\mathrm{\Delta }{G}_{\text{b}}^{\circ }$	RMSDnat	docking score	RMSDMD	$\mathrm{\Delta }{G}_{\text{b}}^{\circ }$
T-1	6.73	−5.5	4.27		7.99	−6.2	1.95	−11.53 ± 2.38
	6.94	−6.5	2.29		1.28	−7.3	1.50	−12.54 ± 1.88
	6.41	−6.3	3.27		6.18	−7.3	2.46
	0.85	−8.2	1.43	−12.04 ± 2.13	2.31	−6.7	1.76	−7.95 ± 0.47
	2.18	−7.5	2.00	−9.08 ± 3.99	6.69	−5.1	4.80
T-2	4.54	−7.5	2.51		4.83	−7.4	1.75	−15.43 ± 1.09
	5.88	−6.5	6.75		1.89	−8.0	1.07	−18.51 ± 1.40
	6.10	−6.9	1.35	−20.30 ± 2.43	7.09	−6.1	7.54
	0.81	−9.7	1.69	−23.25 ± 1.35	5.73	−6.5	6.94
	5.86	−8.1	2.69		6.19	−7.3	1.26	−12.73 ± 2.02
T-3	7.25	−7.8	2.37		6.08	−7.1	2.41
	7.78	−7.2	1.55	−6.29 ± 1.89	5.35	−7.2	2.79
	7.15	−7.2	3.76		1.21	−8.9	0.91	−14.19 ± 1.62
	0.20	−9.4	0.74	−18.95 ± 1.60	5.95	−7.9	1.13	−10.38 ± 1.52
	6.09	−8.8	1.26	−8.17 ± 3.09	4.93	−7.6	1.66	−4.82 ± 1.47
T-4	5.68	−7.9	4.63		5.49	−8.4	2.98
	5.41	−8.2	1.06	−16.38 ± 2.23	6.89	−7.0	1.62	−3.72 ± 2.02
	6.08	−7.9	2.51		6.76	−7.4	4.64
	0.59	−8.6	0.89	−15.88 ± 0.52	0.68	−8.2	1.55	−16.41 ± 1.97
	5.14	−7.9	1.45	−9.57 ± 1.16	4.93	−7.5	3.20
X-1	8.11	−7.7	2.07		6.08	−6.1	3.18
	7.04	−6.6	1.72	−9.36 ± 2.48	7.05	−6.6	3.75
	0.48	−6.9	1.33	−9.78 ± 2.12	5.36	−6.3	2.21
	6.17	−6.4	4.99		4.46	−6.4	1.92	−4.93 ± 2.77
	7.55	−7.0	3.05		6.95	−6.4	4.48

^aRMSD_nat (Å): RMSD of a docked ligand from its native pose, docking score (kcal/mol): binding affinity predicted by AutoDock Vina. RMSD_MD (Å): average ligand RMSD from the initial docked pose during the last 100-ps equilibration MD, $\mathrm{\Delta }{G}_{\text{b}}^{\circ }$