Fig. 5. Higher energy barrier for resolvation of the binding site is observed with 2.
a WaterMap ligand scores based on the ligand displaced waters in the MSM derived metastable state derived conformations. Three structures for each metastable state were evaluated. *P < 0.05 (two-tailed t-test). Weighted average is calculated by using the equilibrium probability (πi) associated for each metastable state as the weight. b Displaced waters by 1 in the 1-S3 conformation I (hydration sites with overlap factor >0.5 with the ligand are shown). 1 is shown with ball and stick representation (nonpolar hydrogens are hidden). c Displaced waters by 2 in the 2-S3 conformation I (hydration sites with overlap factor >0.5 with the ligand are shown). 2 is shown with ball and stick representation (nonpolar hydrogens hidden). b, c The hydration sites are shown in spheres together with their estimated energies (kcal/mol, ΔG relative to bulk water) and are colored with the green-brown-red scale from low to high energy. Source data are provided as a Source Data file.