To gain insight into the thermodynamic changes during the chemical reactions or phase transformation of bioploymers, particularly the unfolding of proteins (or their association) which occurs with exceptionally large enthalpy and entropy changes, a procedure suggested by Benzinger (Benzinger, T, H. Nature (London) 1971, 229, 100), and variously used by Chun (J. Phys. Chem. 1996, 100, 7283. Ibid. 1994, 98, 6851), has been revised in the light of the observations that proteins vitrify gradually on cooling and behave like a glass. Thus a protein retains a finite entropy at 0 K. This makes the method suggested by Benzinger untenable for determining the temperature-independent energy change due to the breaking and reforming of chemical bonds in proteins and other biopolymers during their chemical and physical transformations. The value of the temperature-invariant enthalpy deduced already by this method are underestimated by a term equal to T Delta S-0, i.e., the temperature at which the Gibbs free energy change is zero (or the equilibrium constant is unity), multiplied by the difference between the residual entropy of the two states (or products and reactants). A resolution of the issue of the unusually large enthalpy change on chemical and other transformations in proteins has been given in terms of configurational contributions to the enthalpy and entropy of proteins. These contributions arise from an exceptionally large number of the degrees of molecular freedom in the biopolymer and the diffusion of water and that of the substances added to facilitate protein association or unfolding. The procedure has been illustrated from calculations of several thermodynamic state functions for an orientationally disordered crystal which shares the characteristic behavior of crystalline proteins in as much as the occurrence of molecular configurational freedom and the kinetic freezing of the degree of this configurational freedom, or glasslike transition, is concerned. The calculations and the underlying concepts transcend the details of the molecular structure of a material.