In particular, we investigate the origin of enthalpy-entropy compensation observed for this ligand binding process. The calculations indicate that residues in loop regions at the protein-ligand interface loose flexibility upon ligand binding. The change in vibrational entropy upon binding, determined from the calculated vibrational frequencies, correlates linearly with the entropy of binding. Three translational and three rotational degrees of freedom of the ligand are converted to six vibrational modes in the complex. This causes a gain in vibrational entropy, however, restrictions in the flexibility of protein and ligand atoms lead to a net loss of vibrational entropy.
Residues interacting strongly with the ligand are responsible for the loss of vibrational entropy.
The loss of rotational and translational entropy is about compensated by a gain in hydration entropy. This study clarifies the role entropy plays in ligand binding reactions. Always watch for outdated information. This article first appeared in 1996. This material is designed to support, not replace, the relationship that exists between you and your doctor.