Figure 6.

(a) A comparison of the experimental absolute binding free energies for compounds 16-22 to those obtained by MM/PBSA and the corresponding values calculated by PDLD/S-LRA/β approach (also see Table 3). (b) Illustrating the fact that the MM/PBSA appears to provide reasonable results for some molecules only because of the major overestimate of the entropic effect by comparing the absolute binding free energy calculated by MM/PBSA reported in the literature³¹,³² to the absolute binding free energies calculated by replacing the MM/PBSA entropy with the entropy calculated by the RR method for compounds (16-22). The experimentally determined absolute binding free energies are also provided.