Table 4.

Results of MMPBSA Calculations for Antagonist Ligands Bound to M2R and M3R^a

	ΔG(MMPBSA)
structure	memopt = 1	memopt = 2	memopt = 3	ΔG(exp.)
M3R (QNB)	−28.9	−35.3	−35.7	−13.6
M3R (TIO)	−31.6	−32.3	−32.4	−13.3
M3R (C6B)	−33.4	−36.0	−36.3	−13.3
M2R(QNB)	−46.7	−43.9	−43.9	−13.7
M2R (TIO)	−36.8	−36.8	−36.9	−13.5
M2R (C6B)b	−38.4	−36.2	−36.5	−10.5

^aMMPBSA calculations were carried out using SANDER in MMPBSA.py for the M2R and M3R test system using the uniform, single dielectric membrane model (memopt = 1), the heterogeneous dielectric membrane model with the PCHIP fitting (memopt = 2), and the heterogeneous dielectric membrane model with the spline fitting (memopt = 3). For the uniform, single dielectric membrane model, the membrane dielectric constant was set to 4 while in all three models the protein dielectric constant was set to 2. The experimental binding free energies were obtained from the literature.⁵⁴ The antagonist ligand bound to M2R or M3R is listed in parentheses. All binding free energies are reported in units of kcal/mol.

^bThis was excluded from Figure 8.