Receptor binding empirical approach

Andrews et al. (1984) have adopted a semi-empirical approach to the calculation of binding energy. They fix the loss of translational and rotational entropy in any drug-receptor association to be 14 kcal/mol (the Williams ACj+r term) and partition binding energy AG (defined as a -t-ve quantity) according to equation (11) ... 

This empirical approach would predict, in the absence of any data related to interactions with a molecular target, that because j3-adre-noceptor antagonists lower blood pressure, then any compound that lowers blood pressure is by definition a j3-adrenoceptor antagonist, an absurd conclusion, but one that happened nonetheless. The 1960s saw the development of a number of in vitro biochemical screens that moved the measurement of the RL interaction a little closer to the molecular level. Nonetheless, the major challenge was to develop assays that measured the RL interaction independently of "downstream" events such as enzyme activation and second and third messenger systems. By such means, the ability of a compound to bind to a receptor could be determined on the basis of the SAR and thus provide the chemist with a more direct means to model the RL interaction. 

Another way to facilitate the comparison of the binding affinity among a number of rather different ligands is the semi-empirical linear response approach (51-56). This method assumes the binding affinity, AG, between a ligand-receptor pair to be approximated by the relation... 

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