Figure 1
(a) The relationship between the fold reduction of the equilibrium concentrations of AB (in the dimerization reaction discussed in the text) and the association constant K following a 1,000-fold dilution of A0 and B0. Two different initial concentrations of A and B have been considered (1 μM and 1 nM). Calculations were made using the analytical solution of the equation: fold reduction = (ABeq(for A0,B0))/(ABeq(for A0/1,000,B0/1,000)). Note that both axes are logarithmic. It is easy to see that the differences in the yield of AB after dilution depend on the initial input concentrations and are enormous for low K values (weak complexes). These differences, however, decrease as K increases (tight complexes). Notice that for lower initial concentrations of A and B the curve moves towards the right, and higher K values will be required to obtain a similar fold-reduction relative to the situation where the initial monomer concentrations are higher. Fusion of A and B is intuitively equivalent to increasing K to infinity or to enormously increasing the amounts of A able to 'see' B. There is a link between K and classical thermodynamic parameters (such as those evoked in [1]) but these parameters are less immediate than the mass-action arguments and are of minor importance for understanding here. (b) The equilibrium concentration of A (or B) and AB as a function of K (M-1) for A0 = B0 = 1 nM. It is clear that for low K the association reaction is very inefficient. As K increases, the concentration of free monomers (physicochemically required to fulfill the constraints of the mass action law but biologically useless) decreases. Fusion of A and B is the best option available to avoid monomer wasting and the diffusional problems mentioned in the text.