Understanding Biochemical Dissociation Constants: A Temporal Perspective
Reversible, noncovalent binding is the first obligatory step in the expression of the function of most biological macromolecules. Both binding and release of ligand should be understood for a full view of the total binding process. Binding interactions can be studied at the structural, equilibrium–thermodynamic, or kinetic level. Most biochemists use dissociation constants, KD, to characterize the strength of the dynamic binding equilibrium. Unfortunately, the multiple-term unit for KD (mol/L) does not convey an intuitive understanding of the strength of the binding interaction, other than the notion that a small KD reflects tight binding. This manuscript describes the need for (from survey data) and use of another parameter, the half-life (t1/2) of the bound complex, as an alternative measure of binding strength. This changes the interpretation of the binding parameter to a more direct and simple interpretation of how long the complex stays intact (t1/2, with units of time) from the more indirect interpretation of the magnitude of KD (with units of mol/L). Deviations from this model arising from restricted accessibility of binding surfaces, facilitated diffusion from electrostatic interactions, and conformational changes are also discussed.
Jakubowski, H. V. Understanding Biochemical Dissociation Constants: A Temporal Perspective. J. Chem. Educ., 2002, 79(8), 968.