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  • Title: Kinetic analysis of cooperative ligand binding: applications to the insulin receptor.
    Author: De Lean A, Rodbard D.
    Journal: Fed Proc; 1980 Jan; 39(1):116-20. PubMed ID: 7351239.
    Abstract:
    We have developed a mathematical model for the kinetics of cooperative binding, assuming a linear relationship between the dissociation rate constant kd' and receptor occupancy, and have extensively explored its properties. Under ideal conditions changes in receptor occupancy by the hormone are coupled to changes in its dissociation rate. However, the correlation between receptor occupancy and the apparent dissociation rate can be obscured or even reversed in the presence of minor nonspecific binding, incomplete separation of bound and free ligand, and/or when there is a short lag period between the true onset of dissociation and measurement of "initial" binding. The present model and computer simulation studies suggest ways to reconcile otherwise conflicting observations. These results provide a basis for improved experimental design, to test the ability of this class of cooperative models to describe hormone binding systems.
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