Thermodynamics of Enzyme Folding and Activity: Theory and Experiment

The thermodynamic cycle--perturbation method is a new theoretical approach for predicting how alterations in molecular structure will change the thermodynamics of any of a large number of possible molecular processes (1–7). The structural alteration might for example be a single-site mutation in a protein or a chemical modification of a drug molecule. The process of interest might be the folding of a protein, the binding of a ligand to a receptor, the association of a repressor protein to an operator region of DNA, etc.; and the thermodynamic quantity to be predicted might be a relative free energy of folding or binding, an entropy or enthalpy of activation, or any other quantity.