Enthalpy of hydrogen bond formation in a protein-ligand binding reaction.

摘要: Abstract Parallel measurements of the thermodynamics (free-energy, enthalpy, entropy and heat-capacity changes) ligand binding to FK506 protein (FKBP-12) in H2O D2O have been performed an effort probe energetic contributions single protein-ligand hydrogen bonds formed reactions. Changing tyrosine-82 phenylalanine FKBP-12 abolishes bond interactions complexes with tacrolimus or rapamycin leads a large apparent enthalpic stabilization both D2O. High-resolution crystallographic analysis reveals that two water molecules bound hydroxyl group unliganded are displaced upon formation complexes. A thermodynamic is presented suggests removal polar atoms from contributes highly unfavorable enthalpy change C=O...HO as they occur processes folding binding. Despite less favorable change, entropic advantage displacing slightly more free-energy reactions wild-type FKBP-12.