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Binding of flexible ligands to macromolecules

An Erratum to this article was published on 10 July 1975


MANY of the small molecules, such as enzyme substrates and inhibitors, hormones and neurotransmitters, the interactions of which with macromolecules are of fundamental importance in biology, may exist in solution in a number of conformations in equilibrium with one another. On the other hand, evidence from crystallographic studies suggests that when bound to a macromolecule these small flexible ligands have a single, well defined, conformation. The formation of such a ligand–macromolecule complex must therefore involve a process of conformational selection, which will influence the binding constant and the kinetics of complex formation. The apparent binding constant will simply be the product of the binding constant for the ‘correct’ conformation of the ligand and the mole fraction of this conformation in solution. The kinetic effects of conformational selection will depend on the mechanism of the binding process, and two contrasting models for this may be considered1,2.

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BURGEN, A., ROBERTS, G. & FEENEY, J. Binding of flexible ligands to macromolecules. Nature 253, 753–755 (1975).

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