The theory of interaction parameters has thus far been based on the free-energy relationships in the formation of ternary complexes formed between a pair of ligands and a protein molecule. The concept has been formulted in terms of a ‘thermodynamic square’ comprised of the free protein, the two binary complexes, and the ternary complex. However, an increasing number of proteins have been found to exist as equilibrium mixtures of two macrostates. The equilibrium constants for such two-state transitions vary quite considerably between the various binary and ternary complexes of a given protein. We show here that the interpretations of interaction parameters in such two-state systems, requiring the use of a ‘thermodynamic cube’, are much more complex than those based on the classic ‘thermodynamic square’ commonly employed. We demonstrate the use of enthalpies of interaction and heat capacities of interaction to analyze the source of observed free enerigies of interaction in such systems. Specifically, we find that measured negative interaction parameters may arise simply from the inability of a system to achieve all of the positive component effects anticipated by the conventional formulation.
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Fisher, H.F., Singh, N. The meaning of interaction parameters in two-state protein complexes. Journal of Biological Physics 17, 213–220 (1990). https://doi.org/10.1007/BF00418883
- Interaction parameters
- two-state transition
- free energy