Binding free energies and individual energy components predicted by MM/PBSA (kcal mol⁻¹).

System	ΔEele	ΔEvdW	ΔGPB	ΔGSA	ΔGnonpolara	ΔGpolarb	ΔGbind,PB	pIC50
ERK2/1	−74.22	−54.34	104.88	−9.10	−63.44	30.66	−32.78	5.58
ERK2/1a	−73.13	−52.84	104.97	−7.64	−60.48	31.84	−28.64	5.68
ERK2/1b	47.81	−53.31	98.02	−8.11	−61.42	30.21	−31.21	5.09
ERK2/2	−52.89	−61.56	94.26	−8.86	−70.42	41.37	−29.05	5.36
ERK2/2a	−59.32	−51.26	91.88	−9.00	−60.26	32.56	−27.70	4.00
ERK2/2b	−66.49	−54.66	103.00	−8.61	−63.27	36.51	−26.76	4.30
ERK2/3	−66.77	−50.93	98.08	−8.74	−59.67	33.36	−26.31	4.70
ERK2/3a	−64.72	−57.09	105.51	−8.52	−65.61	40.79	−24.82	5.26
ERK2/3b	−51.96	−69.80	92.47	−8.68	−78.48	40.51	−29.28	4.70
ERK2/3c	−63.20	−67.42	114.09	−8.53	−75.95	46.67	−28.69	4.92
ERK2/3d	−58.44	−61.09	95.26	−7.92	−69.01	36.82	−32.19	5.03
ERK2/4	−78.24	−65.10	117.55	−8.46	−73.56	39.31	−34.26	6.39
ERK2/4a	−68.93	−64.12	103.23	−7.97	−72.09	34.30	−37.79	7.00
ERK2/4b	−67.89	−73.49	104.63	−8.63	−82.12	43.37	−38.75	5.75
ERK2/5	−57.65	−65.72	93.18	−8.92	−74.64	35.54	−39.10	5.74
ERK2/5a	−58.80	−64.89	96.57	−9.07	−73.96	37.77	−36.19	5.57
ERK2/6	−64.70	−71.80	104.94	−8.55	−80.35	40.24	−40.11	6.89
ERK2/7	−67.42	−73.76	107.69	−8.41	−82.17	40.27	−40.10	7.00
ERK2/7a	−58.99	−64.88	96.46	−9.21	−74.09	37.47	−36.62	5.75
ERK2/7b	−73.65	−68.07	112.38	−9.10	−77.17	38.73	−38.44	5.74
ERK2/7c	−58.29	−58.20	97.91	−7.62	−65.82	39.32	−26.50	5.57
ERK2/8	−56.50	−63.96	94.39	−7.97	−71.93	37.89	−34.04	5.80
ERK2/9	−68.36	−58.89	108.38	−7.91	−66.80	35.02	−31.78	4.73
ERK2/9a	−67.01	−51.33	99.44	−8.33	−59.66	32.43	−27.23	4.30
ERK2/9b	−70.46	−71.94	111.46	−8.93	−80.87	41.00	−39.87	5.44
ERK2/9c	−55.37	−63.32	88.74	−8.22	−71.54	33.37	−38.17	4.93
ERK2/9d	−71.09	−60.30	103.28	−8.10	−68.40	32.19	−26.21	5.60

^aΔG_polar = ΔE_ele + ΔG_PB.

^bΔG_nonpolar = ΔE_vdW + ΔG_SA.