Rose PW.
Abstr Meet Groups Stud Struct AIDS Relat Syst Their Appl Target Drug Des. 1995 Jun 5-7; 9: (unnumbered abstract).
Agouron Pharmaceuticals, Inc., San Diego, CA 92121, USA.
The thermodynamics of ligand binding reactions with the FK506 binding protein (FKBP-12) has been determined by titration calorimetry. We elucidate the relationship between structure and thermodynamics by computational studies on crystal structures of ligand-FKBP-12 complexes. In particular, we investigate the origin of enthalpy-entropy compensation observed for this ligand binding process. Normal mode analysis was performed on the crystal structures of ligand-FKBP-12 complexes and the unbound protein and ligands. 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.
Publication Types:
Keywords:
- Crystallization
- Entropy
- Ligands
- Pliability
- Proteins
- Tacrolimus Binding Protein 1A
- Tacrolimus Binding Proteins
- Thermodynamics
Other ID:
UI: 102215230
From Meeting Abstracts