Table 1.

Thermodynamic and structural parameters of water molecules at the catalytic site (ligand binding) in different conformations of MD simulated structures of Mpro protein.

MD-Structures	Conserved Water Sites	Reference Residue ID	EWP	½ EW−bulk	ΔE	WFP	J
Native	W3	H41, D187, H164	−18.75	−3.50	−15.25	24.00	−1.90
HCQ	W3	H41, D187, H164	−20.73	0.15	−20.88	26.00	−1.95
Indacaterol	W4	H41	−8.27	−4.29	−2.82	6.16	−1.09
	W5	W4, W6	1.60	−6.14	7.74	1.89	−0.38
	W6	S46, LIG	−1.92	−5.45	2.37	3.58	−0.76
ZINC28706440	W7	H41, C145	−10.49	−3.61	−6.88	11.00	−1.43

E_WP, Conserved Water with protein; E_W−bulk; Conserved Water with bulk water; LIG; indacaterol.

*The calculation is defined previously in Methods in Section 2.5. The energies (E_WP, E_W−bulk, ΔE, WFP, and J interaction value) are in kcal/mol.