Enhancement of Electrostatic Binding Through Cooperative Interactions: Enthalpy/Entropy Compensation and Peptide—Peptide Recognition

Abstract

In recent work we have established a fundamental relationship between the cost in entropy of an association between two entities A and B, involving one- and two-point interactions in the gas phase, or in non-polar solvents, to give a complex A,B, as a function of the exothermicity of the interaction between them (1). While there is a limit to the adverse entropy of a bimolecular association in terms of the loss of translational and overall rotational freedom (ca 50 to 60 kJ/mol for TΔS° in solution at 298 K) (2), the exothermicity of an interaction can increase far beyond the exothermicity at which the limiting cost in entropy is approached. We have proposed, and subsequently justified on the basis of a large body of experimental data from many laboratories (for example, see Figure 1A), that the enthalpic benefit versus entropie cost of associations of the type stipulated above have the general form shown in Figure 1B (1). We emphasise the approximate form of the curve; the precise entropie cost of an association is dependent on many variables such as mass, density of vibrational states and the shape of the potential energy well in which the associated species lies. In complex systems where the possibility arises that internal rotations are also restricted within the associating species, then the limiting entropie cost will be higher with the curve displaced to the right. The loss of entropy illustrated by Figures 1A and 1B reflects only loss of translational and overall rotational freedom upon association. The data clearly show that associations with small exothermicities can result in remarkably small adverse entropy changes.