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 Concept Videos

G Protein-coupled Receptors01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
The Two-State Receptor Model01:29

The Two-State Receptor Model

The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with one...

You might also read

Related Articles

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

Sort by
Same author

Mechanistic Dissection of Conformational Transition of Bicyclic Peptide via Molecular Modeling and Deep Learning.

bioRxiv : the preprint server for biology·2026
Same author

Quantifying Spatially Resolved Hydration Thermodynamics Using Grid Inhomogeneous Solvation Theory [Article v1.0].

Living journal of computational molecular science·2026
Same author

Revealing imatinib-kinase specificity via analyzing changes in protein dynamics and computing molecular binding affinity.

bioRxiv : the preprint server for biology·2026
Same author

Structure-Based Experimental Datasets for Benchmarking Protein Simulation Force Fields [Article v1.0].

Living journal of computational molecular science·2026
Same author

Relative BAT: An Automated Tool for Relative Binding Free Energy Calculations by the Separated Topologies Approach.

Journal of chemical information and modeling·2025
Same author

Assessment of Pharmaceutical Protein-Ligand Pose and Affinity Predictions in CASP16.

Proteins·2025

Related Experiment Video

Updated: Jul 18, 2026

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells
14:02

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells

Published on: April 9, 2018

Concepts in receptor optimization: targeting the RGD peptide.

Wei Chen1, Chia-en Chang, Michael K Gilson

  • 1Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, 9600 Gudelsky Drive, Rockville, Maryland 20850, USA.

Journal of the American Chemical Society
|April 6, 2006
PubMed
Summary

Designing synthetic receptors with high binding affinity is challenging. This study reveals that opposing forces like desolvation and entropy limit receptor efficiency, but proteinlike affinity is achievable for low molecular weight receptors.

More Related Videos

Preparing a 68Ga-labeled Arginine Glycine Aspartate (RGD)-peptide for Angiogenesis
07:48

Preparing a 68Ga-labeled Arginine Glycine Aspartate (RGD)-peptide for Angiogenesis

Published on: January 7, 2019

Screening Peptides that Activate MRGPRX2 using Engineered HEK Cells
12:38

Screening Peptides that Activate MRGPRX2 using Engineered HEK Cells

Published on: November 6, 2021

Related Experiment Videos

Last Updated: Jul 18, 2026

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells
14:02

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells

Published on: April 9, 2018

Preparing a 68Ga-labeled Arginine Glycine Aspartate (RGD)-peptide for Angiogenesis
07:48

Preparing a 68Ga-labeled Arginine Glycine Aspartate (RGD)-peptide for Angiogenesis

Published on: January 7, 2019

Screening Peptides that Activate MRGPRX2 using Engineered HEK Cells
12:38

Screening Peptides that Activate MRGPRX2 using Engineered HEK Cells

Published on: November 6, 2021

Area of Science:

  • Computational chemistry
  • Molecular modeling
  • Biophysics

Background:

  • Designing synthetic receptors with high binding affinity is difficult.
  • Achieving proteinlike affinities in low molecular weight receptors remains a significant challenge.

Purpose of the Study:

  • To understand limitations in designing high-affinity synthetic receptors.
  • To explore the upper limits of receptor affinity using computational methods.
  • To analyze the binding of the RGD peptide to synthetic receptors.

Main Methods:

  • Utilized novel computational methods, including the M2 modeling method.
  • Employed a de novo design algorithm to generate synthetic receptors in silico.
  • Analyzed binding forces, desolvation penalties, and entropic costs.

Main Results:

  • Identified systematic opposition between binding forces and desolvation/entropy penalties.
  • Found strong correlations between electrostatic attractions and desolvation penalties.
  • Observed correlations between binding energy and configurational entropy costs.
  • Demonstrated that proteinlike affinity is achievable for low molecular weight receptors.
  • Discovered that macrocyclization can unexpectedly increase binding entropy costs.

Conclusions:

  • Forces driving binding are counteracted by desolvation and entropy costs, explaining design difficulties.
  • Developed measures of receptor efficiency to assess performance.
  • Computational analysis suggests low molecular weight receptors can reach proteinlike affinities.
  • Macrocyclization's impact on entropy requires careful consideration in receptor design.