Cohen's Conjecture, Howard's Hypothesis, and Ptashne's Ptruth: an exploration of the relationship between affinity and specificity

Both affinity and specificity for ligands directly influence the functions of biological macromolecules. Some investigators assume that there is a consistent relationship between the affinity of a receptor molecule for its cognate ligand(s) and the specificity of that same receptor (affinity for cognate versus non-cognate ligands). However, analysis of the range of physical factors that account for changes in affinity, in any particular direction and to any particular degree, of a receptor for a cognate ligand suggests strongly that such factors can have disparate effects on the affinities of the receptor for different non-cognate ligands. Therefore, there can be no simple relationship between affinity and specificity as defined by relative binding of the receptor to cognate and non-cognate ligands.