Thermodynamic parameters of ligand-receptor interactions: computation and error margins

A semiempirical relationship describing the temperature function of ligand-receptor dissociation constants (Kd), derived from heat capacities of the system in equilibrium, is suggested for computation of the standard enthalpy (delta H degree) and standard entropy (delta S degree) changes in equilibrium. The use of the linear expression (called Gibbs-van't Hoff equation) may lead to inaccurate results when heat capacity Cp displays a considerable temperature dependence. The accuracy of Kd, delta H degree and delta S degree has been studied by simulation experiments. In the case of Kd, deviations of computed from "true" values are determined by both the accuracy of experimental data used for its estimation, and by the shape of the binding isotherm (for instance, by Hill coefficients or by the presence of low affinity sites). As a rule, if errors of bound ligand measurements are greater than 20 per cent, Kd estimates ought to be considered as less reliable. However, computations of delta H degree and delta S degree that use such Kd values, are more correct, probably due to an error compensation. The suggested nonlinear temperature function of Kd enables an estimate of the heat capacity of the system and its temperature dependence.