Table 2: Ligand-residue MM-GBSA interaction energies (kcal/mol).

PubChem IDs are listed for the two bio-actives. The common hotspots for all the ligands are: HIS41, MET49, ASN142, HIS164, MET165, GLU166, and GLN189.

Residue ID	Residue Type	Co-crystal Ligand	Neutral Approved Drug					Charged Approved Drug			Bioactive
			DB08889	DB12329	DB00385	DB01601	DB11574	DB01082	DB03147	DB11184	23727975	88143175
24	THR	−0.09	−0.15	−0.04	−0.04	−0.06	−0.93	−0.01	−0.10	−0.28	−0.08	−1.40
25	THR	−1.51	−1.50	−0.15	−0.55	−1.56	−4.04	−0.10	−1.60	−3.18	−0.64	−3.68
26	THR	−0.61	−0.90	−0.17	−0.21	−0.27	−6.19	−0.07	−3.08	−4.51	−0.17	−4.33
27	LEU	−3.74	−1.24	−0.52	−1.03	−1.26	−2.20	−0.71	−2.60	−2.48	−0.25	−1.64
28	ASN	−4.78	−0.09	−0.03	−0.06	−0.05	−0.19	−0.10	−0.22	−0.07	−0.08	−0.14
39	PRO	−0.84	−0.19	−0.09	−0.13	−0.24	−0.20	−0.31	−0.32	−0.11	−0.13	−0.17
41	HIS	−6.74	−6.56	−2.93	−5.41	−3.58	−3.79	−5.38	−7.78	−4.18	−3.02	−2.99
44	CYS	−1.02	−0.13	−0.09	−0.07	−1.37	−0.67	−0.05	−2.50	−0.37	−0.09	−0.43
45	THR	−0.60	−0.32	−0.24	−0.06	−1.10	−0.59	−0.02	−1.76	−0.26	−0.17	−0.47
46	SER	−0.91	−1.79	−1.54	−0.62	−4.26	−1.45	−0.07	−3.53	−1.28	−1.79	−2.70
49	MET	−4.39	−2.37	−3.14	−2.14	−5.57	−4.18	−1.07	−5.46	−2.23	−2.17	−3.93
52	PRO	−0.76	−0.06	−0.08	−0.08	−0.03	−0.19	−0.01	−0.07	−0.02	−0.06	−0.04
54	TYR	−0.65	−0.12	−0.45	−0.22	−0.14	−0.54	−0.15	−0.17	−0.11	−0.09	−0.05
119	ASN	−0.16	−0.02	−0.07	−0.09	−0.02	−1.41	−0.02	−0.44	−0.05	−0.02	−0.05
140	PHE	−0.19	−0.98	−0.04	−0.09	−0.02	−0.06	−0.80	−0.08	−0.17	−0.35	−1.81
141	LEU	−0.28	−1.16	−0.10	−0.23	−0.03	−0.09	−1.00	−0.05	−0.27	0.49	−2.64
142	ASN	−3.50	−4.39	−3.46	−3.66	−0.59	−2.89	−6.70	−4.56	−4.58	−5.50	−6.82
143	GLY	−2.23	−0.75	−0.96	−0.36	−0.37	−2.34	−1.87	−3.77	−1.50	−2.48	−2.11
144	SER	−13.05	−1.42	−0.12	−0.17	−0.10	−0.31	−2.09	−1.19	−0.60	−5.29	−2.33
145	CYS	−66.34	−3.22	−0.71	−1.53	−1.59	−2.09	−3.95	−4.27	−1.50	−2.96	−3.83
146	GLY	−10.20	−0.02	−0.01	−0.03	−0.03	−0.02	−0.06	−0.04	−0.03	−0.06	−0.06
147	SER	−0.64	−0.05	−0.01	−0.02	−0.01	−0.02	−0.06	−0.05	−0.02	−0.02	−0.10
163	HIS	−3.88	−1.65	−0.13	−0.38	−0.14	−0.17	−2.82	−0.40	−0.63	−1.22	−1.18
164	HIS	−3.92	−4.89	−1.41	−3.65	−1.80	−1.56	−5.26	−5.44	−1.30	−2.51	−2.53
165	MET	−5.49	−7.83	−4.16	−4.63	−3.46	−3.65	−5.27	−4.91	−4.74	−6.50	−4.43
166	GLU	−7.31	−6.67	−6.05	−6.76	−0.82	−1.77	−17.06	−6.44	−4.91	−14.38	−23.80
167	LEU	−1.67	−1.36	−1.26	−2.11	−0.63	−1.28	−1.92	−0.78	−1.31	−2.06	−1.16
168	PRO	−2.73	−1.17	−1.11	−2.50	−1.26	−2.66	−2.55	−0.35	−1.18	−2.15	−0.91
170	GLY	−0.05	−0.08	−0.01	−0.03	−0.02	−0.07	−0.54	−0.01	−0.03	−0.11	−0.17
172	HIS	−0.17	−1.15	−0.09	−0.18	−0.07	−0.10	−0.70	−0.09	−0.33	−1.07	−1.07
186	VAL	−0.31	−0.61	−0.28	−0.18	−0.33	−0.37	−0.09	−0.60	−0.27	−0.28	−0.29
187	ASP	−1.49	−1.29	−2.24	−1.36	−3.74	−1.90	−2.85	−2.05	−1.64	−1.34	−1.17
188	ARG	−1.60	−2.04	−1.94	−1.74	−1.68	−2.34	−0.57	−1.75	−1.85	−1.82	−1.17
189	GLN	−5.25	−13.79	−5.90	−11.52	−8.10	−7.69	−2.27	−6.11	−8.78	−10.07	−6.93
190	THR	−1.42	−1.56	−3.94	−2.43	−1.55	−3.84	−0.05	−1.08	−3.22	−0.99	−0.60
191	ALA	−1.65	−2.48	−0.23	−0.68	−1.52	−1.56	−0.03	−0.16	−0.81	−0.46	−0.13
192	GLN	−2.24	−3.48	−3.96	−2.28	−1.13	−1.80	−0.16	−1.23	−6.28	−1.72	−0.75