Thermodynamics of local linkage effects. Contracted partition functions and the analysis of site-specific energetics.

A thermodynamic theory is presented for the description of local, site-specific linkage effects in biological macromolecules. The theory is developed from a basic isomorphism involving the intensive quantities of a thermodynamic system at equilibrium. Local linkage effects can be cast within the same mathematical framework as the one used in the statistical thermodynamic theory of global linkage effects involving different ligands. In addition to this parallel, local linkage effects give rise to apparent violations of thermodynamic stability that can be of relevance in energy transduction phenomena. It is also shown that the canonical partition function for the macromolecule as a whole can be expressed in terms of contracted partition functions that greatly simplify calculations of the relevant thermodynamic properties of individual sites. Site-specific Hill plots, partition coefficients and free energies of linkage are introduced and their properties discussed in connection with those of analogous global quantities. Calculation of the free energies of linkage for human hemoglobin yields a minimal phenomenological scheme for the coupling among subunits.