Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Agonist induction, conformational selection, and mutant receptors.

Jesús Giraldo1

  • 1Grup de Modelització Estructural i Funcional de Sistemes Biològics, Institut de Neurociències and Unitat de Bioestadística, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain. jesus.giraldo@uab.es

FEBS Letters
|January 7, 2004
PubMed
Summary

Distinguishing between agonist induction and conformational selection receptor activation models is challenging. This study demonstrates the thermodynamic impossibility of differentiating these pathways and proposes a double two-state model for quantitative analysis of receptor mutation effects.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

In silico prediction of novel effective combinational treatment of chronic pain in individual patients: A joint white paper of the H2020 QSPainRelief consortium.

British journal of pharmacology·2026
Same author

Identification of Subtype-Selective Binding Sites in the Opioid Receptor Family.

Journal of chemical information and modeling·2026
Same author

Allosteric activation of the glutamate receptor mGlu2 by the serotonin receptor 5-HT<sub>2A</sub>.

Nature communications·2026
Same author

Drug-target residence time: Analyzing cooperativity effects in G protein-coupled receptors by mathematical modeling and molecular dynamics simulations.

Current opinion in structural biology·2026
Same author

A mathematical formalism to quantify drug-target residence time.

Biochemical pharmacology·2025
Same author

Structural Determinants of Buprenorphine Partial Agonism at the μ-Opioid Receptor.

Journal of chemical information and modeling·2025

Area of Science:

  • Pharmacology
  • Biophysics
  • Computational Biology

Background:

  • Current receptor activation models include agonist induction and conformational selection.
  • The relative importance of these mechanisms remains a subject of debate.
  • Thermodynamic approaches have been used to study ligand-receptor interactions.

Purpose of the Study:

  • To demonstrate the thermodynamic impossibility of distinguishing between agonist induction and conformational selection.
  • To analyze the impact of receptor mutations on ligand-receptor equilibria.
  • To introduce and validate a refined two-state model for receptor agonism.

Main Methods:

  • Thermodynamic analysis of receptor activation mechanisms.
  • Derivation of pharmacological equations for a double two-state model.

Related Experiment Videos

  • Simulations using the developed two-state model.

    • Main Results:

    • It is thermodynamically impossible to distinguish between agonist induction and conformational selection.
    • The study discusses how receptor mutations affect equilibrium constants.
    • The double two-state model provides a framework for quantitative assessment.

    Conclusions:

    • The double two-state model of agonism is valuable for quantitatively assessing pharmacological activity changes after receptor mutation.
    • This model can help resolve controversies in receptor activation mechanisms.
    • Further research can utilize this model to understand complex receptor dynamics.