Dose-Response Visualiser

Affinity is a measure of the strength of binding of a drug to a receptor (both agonists and antagonists have affinity), and depends on the existence of chemical forces of attraction between the agonist and the receptor binding site (e.g. most commonly ionic bonds, hydrogen bonds, van der Waals forces). The strength of binding (affinity) depends upon the respective 3-D structures of the agonist and binding site – the strength of binding dissipates markedly as the distance between the agonist and binding site increases. High affinity agonists bind to binding sites at low concentrations, whereas low affinity agonists bind at higher concentrations. The affinity of ligands (agonists and antagonists) can be quantitated using the Equilibrium Dissociation Constant (K_A), which is the concentration of ligand needed to occupy (bind to) 50% of receptors. K_A is also the ratio of the rate the ligand (agonist or antagonist) leaves the receptor binding site (k_off) and the rate it approaches the receptor binding site (k_on). The K_A value is inversely proportional to the affinity (high affinity ligands have low K_A values) and is typically measured in drug binding assays (plots of [ligand] versus fractional receptor occupancy). As the [ligand] increases the fraction of receptor bound increases nonlinearly (rectangular hyperbolic function) to form a maximal asymptote (from which R_T can be determined). Colloquially, “affinity is what brings the drug to the receptor”.

Intrinsic Efficacy is the property of the agonist that enables it, once bound, to change the conformation of the receptor (activation), such that it alters the activity of downstream signalling pathways to produce a change in cellular activity. Efficacy is measured in relative terms, having no absolute scale – but different ligands have clearly different efficacies – full agonists have higher efficacies than partial agonists, and antagonists typically have no efficacy (bind to but don’t activate the receptor). Thus, different agonists have different inherent capacities to induce a response, and equal cellular responses can be achieved by different fractional receptor occupancies. Colloquially, efficacy is “what the drug does once it binds to the receptor”.

Receptor Density is the total number of receptors, expressed in terms of unit area of membrane, or per cell, or per unit mass of protein. Proportional to the quantity B_max (the maximal specific binding of a ligand, often expressed in units of mol ligand/mg protein, or ligands bound/cell) measured in radioligand binding studies. The relationship between B_max and N is influenced by the number of ligand binding sites possessed by each receptor. For most receptors there is one binding site for the endogenous agonist, although for ligand-gated ion channels (e.g. nicotinic acetylcholine receptor), this is generally more than one.

Coupling Efficiency is a cell-dependent parameter describing the efficiency of the signalling pathways that couple (link) the activated receptor to the measured effect. Some cells have high coupling efficiencies, meaning that activation of a relatively small number of receptors can lead to a large cellular response. Other cells may have low coupling efficiencies (perhaps due to low expression / activity of a key signalling pathway component) and high levels of receptor activation may produce relatively small cellular responses.

Affinity is a measure of the strength of binding of a drug to a receptor (both agonists and antagonists have affinity), and depends on the existence of chemical forces of attraction between the agonist and the receptor binding site (e.g. most commonly ionic bonds, hydrogen bonds, van der Waals forces). The strength of binding (affinity) depends upon the respective 3-D structures of the agonist and binding site – the strength of binding dissipates markedly as the distance between the agonist and binding site increases. High affinity agonists bind to binding sites at low concentrations, whereas low affinity agonists bind at higher concentrations. The affinity of ligands (agonists and antagonists) can be quantitated using the Equilibrium Dissociation Constant (K_A), which is the concentration of ligand needed to occupy (bind to) 50% of receptors. K_A is also the ratio of the rate the ligand (agonist or antagonist) leaves the receptor binding site (k_off) and the rate it approaches the receptor binding site (k_on). The K_A value is inversely proportional to the affinity (high affinity ligands have low K_A values) and is typically measured in drug binding assays (plots of [ligand] versus fractional receptor occupancy). As the [ligand] increases the fraction of receptor bound increases nonlinearly (rectangular hyperbolic function) to form a maximal asymptote (from which R_T can be determined). Colloquially, “affinity is what brings the drug to the receptor”.

Intrinsic Efficacy is the property of the agonist that enables it, once bound, to change the conformation of the receptor (activation), such that it alters the activity of downstream signalling pathways to produce a change in cellular activity. Efficacy is measured in relative terms, having no absolute scale – but different ligands have clearly different efficacies – full agonists have higher efficacies than partial agonists, and antagonists typically have no efficacy (bind to but don’t activate the receptor). Thus, different agonists have different inherent capacities to induce a response, and equal cellular responses can be achieved by different fractional receptor occupancies. Colloquially, efficacy is “what the drug does once it binds to the receptor”.

Receptor Density is the total number of receptors, expressed in terms of unit area of membrane, or per cell, or per unit mass of protein. Proportional to the quantity B_max (the maximal specific binding of a ligand, often expressed in units of mol ligand/mg protein, or ligands bound/cell) measured in radioligand binding studies. The relationship between B_max and N is influenced by the number of ligand binding sites possessed by each receptor. For most receptors there is one binding site for the endogenous agonist, although for ligand-gated ion channels (e.g. nicotinic acetylcholine receptor), this is generally more than one.

Coupling Efficiency is a cell-dependent parameter describing the efficiency of the signalling pathways that couple (link) the activated receptor to the measured effect. Some cells have high coupling efficiencies, meaning that activation of a relatively small number of receptors can lead to a large cellular response. Other cells may have low coupling efficiencies (perhaps due to low expression / activity of a key signalling pathway component) and high levels of receptor activation may produce relatively small cellular responses.

Affinity is a measure of the strength of binding of a drug to a receptor (both agonists and antagonists have affinity), and depends on the existence of chemical forces of attraction between the agonist and the receptor binding site (e.g. most commonly ionic bonds, hydrogen bonds, van der Waals forces). The strength of binding (affinity) depends upon the respective 3-D structures of the agonist and binding site – the strength of binding dissipates markedly as the distance between the agonist and binding site increases. High affinity agonists bind to binding sites at low concentrations, whereas low affinity agonists bind at higher concentrations. The affinity of ligands (agonists and antagonists) can be quantitated using the Equilibrium Dissociation Constant (K_A), which is the concentration of ligand needed to occupy (bind to) 50% of receptors. K_A is also the ratio of the rate the ligand (agonist or antagonist) leaves the receptor binding site (k_off) and the rate it approaches the receptor binding site (k_on). The K_A value is inversely proportional to the affinity (high affinity ligands have low K_A values) and is typically measured in drug binding assays (plots of [ligand] versus fractional receptor occupancy). As the [ligand] increases the fraction of receptor bound increases nonlinearly (rectangular hyperbolic function) to form a maximal asymptote (from which R_T can be determined). Colloquially, “affinity is what brings the drug to the receptor”.

Intrinsic Efficacy is the property of the agonist that enables it, once bound, to change the conformation of the receptor (activation), such that it alters the activity of downstream signalling pathways to produce a change in cellular activity. Efficacy is measured in relative terms, having no absolute scale – but different ligands have clearly different efficacies – full agonists have higher efficacies than partial agonists, and antagonists typically have no efficacy (bind to but don’t activate the receptor). Thus, different agonists have different inherent capacities to induce a response, and equal cellular responses can be achieved by different fractional receptor occupancies. Colloquially, efficacy is “what the drug does once it binds to the receptor”.

Receptor Density is the total number of receptors, expressed in terms of unit area of membrane, or per cell, or per unit mass of protein. Proportional to the quantity B_max (the maximal specific binding of a ligand, often expressed in units of mol ligand/mg protein, or ligands bound/cell) measured in radioligand binding studies. The relationship between B_max and N is influenced by the number of ligand binding sites possessed by each receptor. For most receptors there is one binding site for the endogenous agonist, although for ligand-gated ion channels (e.g. nicotinic acetylcholine receptor), this is generally more than one.

Coupling Efficiency is a cell-dependent parameter describing the efficiency of the signalling pathways that couple (link) the activated receptor to the measured effect. Some cells have high coupling efficiencies, meaning that activation of a relatively small number of receptors can lead to a large cellular response. Other cells may have low coupling efficiencies (perhaps due to low expression / activity of a key signalling pathway component) and high levels of receptor activation may produce relatively small cellular responses.

The Cooperativity Factor α indicates the maximum effect produced by the allosteric antagonist on agonist affinity – a value of 0.1 indicates that the allosteric antagonist can produce up to a 10-fold reduction in agonist affinity. Observe the effects of changing the affinity and/or cooperativity factor (α) of the Allosteric Antagonist on the shape and position of the Agonist dose-response curve by moving the red slider along the grey bar to the right or left to increase or decrease the value of the characteristic, respectively.

Affinity is a measure of the strength of binding of a drug to a receptor (both agonists and antagonists have affinity), and depends on the existence of chemical forces of attraction between the agonist and the receptor binding site (e.g. most commonly ionic bonds, hydrogen bonds, van der Waals forces). The strength of binding (affinity) depends upon the respective 3-D structures of the agonist and binding site – the strength of binding dissipates markedly as the distance between the agonist and binding site increases. High affinity agonists bind to binding sites at low concentrations, whereas low affinity agonists bind at higher concentrations. The affinity of ligands (agonists and antagonists) can be quantitated using the Equilibrium Dissociation Constant (K_A), which is the concentration of ligand needed to occupy (bind to) 50% of receptors. K_A is also the ratio of the rate the ligand (agonist or antagonist) leaves the receptor binding site (k_off) and the rate it approaches the receptor binding site (k_on). The K_A value is inversely proportional to the affinity (high affinity ligands have low K_A values) and is typically measured in drug binding assays (plots of [ligand] versus fractional receptor occupancy). As the [ligand] increases the fraction of receptor bound increases nonlinearly (rectangular hyperbolic function) to form a maximal asymptote (from which R_T can be determined). Colloquially, “affinity is what brings the drug to the receptor”.

Intrinsic Efficacy is the property of the agonist that enables it, once bound, to change the conformation of the receptor (activation), such that it alters the activity of downstream signalling pathways to produce a change in cellular activity. Efficacy is measured in relative terms, having no absolute scale – but different ligands have clearly different efficacies – full agonists have higher efficacies than partial agonists, and antagonists typically have no efficacy (bind to but don’t activate the receptor). Thus, different agonists have different inherent capacities to induce a response, and equal cellular responses can be achieved by different fractional receptor occupancies. Colloquially, efficacy is “what the drug does once it binds to the receptor”.

Receptor Density is the total number of receptors, expressed in terms of unit area of membrane, or per cell, or per unit mass of protein. Proportional to the quantity B_max (the maximal specific binding of a ligand, often expressed in units of mol ligand/mg protein, or ligands bound/cell) measured in radioligand binding studies. The relationship between B_max and N is influenced by the number of ligand binding sites possessed by each receptor. For most receptors there is one binding site for the endogenous agonist, although for ligand-gated ion channels (e.g. nicotinic acetylcholine receptor), this is generally more than one.

Coupling Efficiency is a cell-dependent parameter describing the efficiency of the signalling pathways that couple (link) the activated receptor to the measured effect. Some cells have high coupling efficiencies, meaning that activation of a relatively small number of receptors can lead to a large cellular response. Other cells may have low coupling efficiencies (perhaps due to low expression / activity of a key signalling pathway component) and high levels of receptor activation may produce relatively small cellular responses.

The Cooperativity Factor β indicates the maximum effect produced by the allosteric antagonist on agonist efficacy. Observe the effects of changing the affinity and/or cooperativity factor (β) of the Allosteric Antagonist on the shape and position of the Agonist dose-response curve by moving the red slider along the grey bar to the right or left to increase or decrease the value of the characteristic, respectively.

Affinity is a measure of the strength of binding of a drug to a receptor (both agonists and antagonists have affinity), and depends on the existence of chemical forces of attraction between the agonist and the receptor binding site (e.g. most commonly ionic bonds, hydrogen bonds, van der Waals forces). The strength of binding (affinity) depends upon the respective 3-D structures of the agonist and binding site – the strength of binding dissipates markedly as the distance between the agonist and binding site increases. High affinity agonists bind to binding sites at low concentrations, whereas low affinity agonists bind at higher concentrations. The affinity of ligands (agonists and antagonists) can be quantitated using the Equilibrium Dissociation Constant (K_A), which is the concentration of ligand needed to occupy (bind to) 50% of receptors. K_A is also the ratio of the rate the ligand (agonist or antagonist) leaves the receptor binding site (k_off) and the rate it approaches the receptor binding site (k_on). The K_A value is inversely proportional to the affinity (high affinity ligands have low K_A values) and is typically measured in drug binding assays (plots of [ligand] versus fractional receptor occupancy). As the [ligand] increases the fraction of receptor bound increases nonlinearly (rectangular hyperbolic function) to form a maximal asymptote (from which R_T can be determined). Colloquially, “affinity is what brings the drug to the receptor”.

Intrinsic Efficacy is the property of the agonist that enables it, once bound, to change the conformation of the receptor (activation), such that it alters the activity of downstream signalling pathways to produce a change in cellular activity. Efficacy is measured in relative terms, having no absolute scale – but different ligands have clearly different efficacies – full agonists have higher efficacies than partial agonists, and antagonists typically have no efficacy (bind to but don’t activate the receptor). Thus, different agonists have different inherent capacities to induce a response, and equal cellular responses can be achieved by different fractional receptor occupancies. Colloquially, efficacy is “what the drug does once it binds to the receptor”.