Structural energetics of peptide recognition: Angiotensin II/antibody binding

摘要: The ability to predict the strength of association peptide hormones or other ligands with their protein receptors is fundamental importance in fields engineering and rational drug design. To form a tight complex between flexible hormone its receptor, large loss configurational entropy must be overcome. Recently, crystallographic structure angiotensin II Fab fragment high affinity monoclonal antibody has been determined (Garcia, K. C., Ronco, P. M., Verroust, J., Brunger, A. T., Amzel, L. M. Three-dimensional an II–Fab at 3 A: Hormone recognition by anti-idiotypic antibody. Science 257:502–507, 1992). In this paper we present study thermodynamics sensitivity isothermal titration calorimetry. results experiments indicate that 30°C binding characterized (1) ΔH −8.9 ± 0.7 kcal mol−1, (2) ΔCp −240 20 cal K−1 (3) release 1.1 0.1 protons per site pH range 6.0–7.3. Using these values previously constant phosphate buffer, ΔG estimated as −11 mol−1 ΔS 6.9 mol−1. calorimetric data favored both enthalpically entropically. These have complemented structural thermodynamic calculations. calculated experimentally quantities are good agreement. Entropically, more than compensated gain from solvent associated hydrophobic effect. Enthalpically, polar interactions (hydrogen bonding). Consequently, problem solved much same way folding unstructured polypeptide chain into globular protein. © 1993 Wiley-Liss, Inc.