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Related Experiment Video

Updated: Jun 5, 2026

Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay

Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay

Published on: March 10, 2020

Inferring mechanisms from dose-response curves.

Carson C Chow¹, Karen M Ong, Edward J Dougherty

¹Laboratory of Biological Modeling, NIDDK/CEB, National Institutes of Health, Bethesda, Maryland, USA.

Methods in Enzymology

|December 29, 2010

Summary

A new theory explains how gene induction follows a first-order Hill dose-response curve (FHDC). This framework predicts mechanisms and cofactor actions in biochemical reactions with FHDC.

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Parallel Interrogation of β-Arrestin2 Recruitment for Ligand Screening on a GPCR-Wide Scale using PRESTO-Tango Assay

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Published on: September 4, 2017

Area of Science:

Biochemistry
Molecular Biology
Systems Biology

Background:

Ligand-mediated gene induction typically follows a first-order Hill equation.
Cofactors and reagents can modulate gene induction potency and maximum activity.
Existing models do not fully explain the underlying mechanisms of these modulations.

Purpose of the Study:

To develop a general theory for first-order Hill dose-response curves (FHDC) in gene induction.
To provide a predictive framework for understanding the mechanisms of cofactors and reagents.
To apply the theory to diverse biochemical reactions exhibiting FHDC.

Main Methods:

Formulation of a general theory based on sequential reactions with dissociable intermediates.
Mathematical modeling of dose-response relationships for gene induction.
Analysis of how cofactors/reagents influence kinetic parameters.

Main Results:

The developed theory accurately describes dose-response curves yielding FHDC.
The theory predicts that weakly bound or transient intermediate complexes are key.
Demonstrated utility in predicting mechanisms and cofactor action sites.

Conclusions:

A novel general theory explains FHDC in ligand-mediated gene induction.
The theory offers a powerful tool for mechanistic prediction in various biochemical systems.
This framework advances the understanding of gene regulation and cofactor function.