THERMODYNAMICS OF PROTEIN-FOLDING AND MOLECULAR RECOGNITION

The successful development of a structural parameterization of the ene rgetics of protein folding has permitted the incorporation of the func tions that define the enthalpy, entropy and heat capacity changes (i.e . the individual components of the Gibbs energy) into a statistical th ermodynamic formalism that describes the equilibrium folding pathway o f a protein. The general approach is to construct with the computer a large ensemble of conformational states, and then derive the most prob able population distribution; i.e. the distribution of states that bes t accounts for a wide array of experimental observables. The accuracy of the approach is evaluated by comparison of predicted and experiment al physical observables. This formalism has allowed the development of a computer program (Virtual Differential Scanning Calorimetry, VDSC) that generates the expected heat capacity function from a PDB data fil e containing the atomic coordinates of a protein; and a second program (CoreFHT) that predicts the NMR derived hydrogen exchange protection factors for individual amino acids.