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The Hill equation reflects the occupancy of macromolecules: the fraction that is saturated or bound by the ligand. [1] [2] [nb 1] This equation is formally equivalent to the Langmuir isotherm. [3] Conversely, the Hill equation proper reflects the cellular or tissue response to the ligand: the physiological output of the system, such as muscle ...
The first description of cooperative binding to a multi-site protein was developed by A.V. Hill. [4] Drawing on observations of oxygen binding to hemoglobin and the idea that cooperativity arose from the aggregation of hemoglobin molecules, each one binding one oxygen molecule, Hill suggested a phenomenological equation that has since been named after him:
This model explains sigmoidal binding properties (i.e. positive cooperativity) as change in concentration of ligand over a small range will lead to a large increase in the proportion of molecules in the R state, and thus will lead to a high association of the ligand to the protein. It cannot explain negative cooperativity.
Hill equation [ edit ] A simple and widely used model for molecular interactions is the Hill equation , which provides a way to quantify cooperative binding by describing the fraction of saturated ligand binding sites as a function of the ligand concentration.
Biological responses to ligand concentrations typically follow a sigmoidal function. The inflection point at which the increase in response with increasing ligand concentration begins to slow is the EC 50, which can be mathematically determined by derivation of the best-fit line. While relying on a graph for estimation is more convenient, this ...
The Hill equation can be used to describe dose–response relationships, for example ion channel-open-probability vs. ligand concentration. [9] Dose is usually in milligrams, micrograms, or grams per kilogram of body-weight for oral exposures or milligrams per cubic meter of ambient air for inhalation exposures. Other dose units include moles ...
In protein-ligand binding, the ligand is usually a molecule which produces a signal by binding to a site on a target protein. The binding typically results in a change of conformational isomerism (conformation) of the target protein. In DNA-ligand binding studies, the ligand can be a small molecule, ion, [1] or protein [2] which binds to the ...
Hofmeyr and Cornish-Bowden first published the reversible form of the Hill equation. [1] The equation has since been discussed elsewhere [ 3 ] [ 4 ] and the model has also been used in a number of kinetic models such as a model of Phosphofructokinase and Glycolytic Oscillations in the Pancreatic β-cells [ 5 ] or a model of a glucose-xylose co ...