Energetics of Macromolecular Recognition

Characterizing the forces that stabilize protein-protein interactions and understanding how these forces operate to yield complexes with 

The most important parameters are AGa, the change in the standard state free enthalpy (or Gibbs energy) of the system on dissociation, its enthalpy component AH, and its entropy component A5d  

The value of AGd is commonly derived from that of the equihbrium constant by applying the classical relation  

Co is the concentration defining the standard state by convention, Co = 1 mol. If Xd has been measured as a function of temperature, AH and A5d can be derived from its temperature dependence by applying the Vant Hoff law. In recent years, isothermal titration microcalorimetry (ITC) has also been used for that purpose. As reviewed by Fisher and Singh (1995) and Ladbury and Chowdhry (1996), microcalorimetry gives direct access to AH and, also, if the titration is performed at several temperatures, to the heat capacity change AGd at constant pressure. The first quantity is proportional to the heat evolved on mixing known amounts of the two components of a complex, and the latter is equal to 

Theoretical analysis aims to rationalize the value of these thermodynamic parameters in terms of the different physical forces involved, at least qualitatively (Gilson et cd., 1997). On the other hand, site-directed mutagenesis and related techniques provide useful estimates of the effect of perturbations, typically by following the removal of individual chemical groups at the interface. Free enthalpy changes can easily be estimated by comparing the dissociation constant of the wild-type complex Kd with that of the variant (which is usually larger than K )  

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