What's an ultimate value of reversible drug binding constant?

Traditional opinion is that a good drug must have a high value of the absolute meaning of the binding energy with target protein in order to prevent the thermal dissociation of the drug-protein complex. In this case an essential deformation of protein arises, which has to be taken into account in developing different models of protein-small molecule and protein-protein interaction, and computing affinity constants in drug discovery in-silico methods. The effect of essential perturbation of protein molecule is ignored in standard computational methods of drug design that can contribute a large mistake to results of calculation, to binding energy, for example.
To demonstrate the existence of the ultimate value of the binding energy two models are considered: macroscopic and microscopic, both giving the same conclusions: the critical value of absolute meaning of binding energy is 50-100kJ/M. If the binding energy exceeds this value, then drug essentially perturbs protein configuration. In a microscopic picture this perturbation is a sequence of irreversible conformational transitions in protein body. In a macroscopic one it is an inelastic deformation of a protein substance. Our estimation agrees with the experimental value (50 kJ /M) of the ultimate energy that can be stored in a protein molecule without its destruction.
The existence of the critical value of binding energy should be accounted in structure based drug design methods where protein molecule is considered in an elastic deformation approximation.

Reference: accepted in Russian Journal of Biophysics, 2008