The computed changes in ligand torsional entropy on binding also are more unfavorable for the constrained ligands than for the corresponding flexible ones (Table , -T ∆∆S ij,bind ). This result is consistent with the prior computational study of this system , which found that the flexible ligands form internal nonbonded interactions which reduce their conformational flexibility when free in solution; while these interactions did not form in the constrained peptides. We wished to compare the configurational entropies of the constrained and flexible ligands in solution, similarly, but a direct comparison cannot be made between ligands with different numbers of torsion angles. Therefore, we recomputed the configurational entropies of free fQ and cQ, this time omitting the χ 2 and χ 3 torsions of the glutamine, to generate entropy estimates based on 17 torsions that chemically match the 17 torsions of fV and cV (Eq 10). Consistent with the prior study, we find that the constrained peptides have greater configurational entropy in solution than the flexible ones, by about 1 kcal/mol (see Supporting Information for details). However, the constrained peptides have less configurational entropy when they are in the binding site, by 0.6 -1.5 kcal/mol (see SI), even though they have fewer stable protein-ligand interactions than the flexible ligands (see above).