TABLE 2

GlyH-101 binding free energy, ΔG_bind, and its components estimated through MM-GB/SA analysis for wt and F342A CFTRs, without and with a membrane

Analyses were performed with eq. 1, ΔG_bind = ΔE_lig + ΔG_solv − TΔS_conf + E_vdw + E_es + ΔE_PTN, where ΔE_lig and ΔE_PTN are changes (upon ligand binding) in the intramolecular strains of the ligand and protein, respectively, ΔG_solv is the total desolvation penalty for the ligand and protein, TΔS_conf is the ligand conformational penalty, and E_vdw and E_es are the van der Waals and electrostatic energies, respectively.

CFTR	ΔE_lig	ΔE_PTN	E_vdw + E_es + ΔG_solv	−TΔS_conf	ΔG_bind
	kcal/mol	kcal/mol	kcal/mol	kcal/mol	kcal/mol
Without membrane
wt	4.68	6.89	−21.2	1.05	−8.54
F342A	3.90	4.04	−21.6	1.05	−12.6
wt − F342A	0.78	2.85	0.42	0.0	4.0
With membrane
wt	4.68	6.88	−19.8	1.05	−7.23
F342A	3.92	4.05	−20.4	1.05	−11.4
wt − F342A	0.76	2.82	0.54	0.0	4.1