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

Ligand Binding Sites02:40

Ligand Binding Sites

15.1K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
15.1K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

5.6K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
5.6K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

4.1K
4.1K
Metal-Ligand Bonds02:51

Metal-Ligand Bonds

24.3K
The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
24.3K
Protein Dynamics in Living Cells01:19

Protein Dynamics in Living Cells

2.7K
Different fluorescence-based techniques are used to study the protein dynamics in living cells. These techniques include FRAP, FRET, and PET.
Fluorescent recovery after photobleaching (FRAP) is a fluorescent-protein-based detection technique used to quantify protein movement rates within the cell. This method exposes a small portion of the cell to an intense laser beam. The laser beam causes permanent photobleaching of the fluorophore-tagged proteins in the exposed region. As the bleached...
2.7K
Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

14.5K
Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
14.5K

You might also read

Related Articles

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

Sort by
Same author

A functional map of CDK-drug interactions at single amino acid resolution.

bioRxiv : the preprint server for biology·2025
Same author

Towards directed therapy for fusion-positive rhabdomyosarcoma.

Pharmacology & therapeutics·2025
Same author

Small molecule modulators of TOX protein re-invigorate T cell activity.

bioRxiv : the preprint server for biology·2025
Same author

Chemical Probe Discovery for DEAD-Box RNA-Binding Protein DDX21 Using Small-Molecule Microarrays.

ACS chemical biology·2025
Same author

At The Interface: Small-Molecule Inhibitors of Soluble Cytokines.

Chemical reviews·2025
Same author

Targeted degradation of CDK9 potently disrupts the MYC-regulated network.

Cell chemical biology·2025

Related Experiment Video

Updated: Feb 3, 2026

Ligand Nano-cluster Arrays in a Supported Lipid Bilayer
10:34

Ligand Nano-cluster Arrays in a Supported Lipid Bilayer

Published on: April 23, 2017

7.3K

An Array-Based Ligand Discovery Platform for Proteins With Short Half-Lives.

Becky S Leifer1, Shelby K Doyle2, André Richters1

  • 1David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States; Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge, MA, United States; The Broad Institute of MIT and Harvard, Cambridge, MA, United States.

Methods in Enzymology
|November 5, 2018
PubMed
Summary

Researchers developed a new method for drug discovery targeting difficult proteins. This protocol uses in vitro translation with array-based screening to find ligands for short-lived, "undruggable" therapeutic targets.

Keywords:
Chemical screeningHigh-throughput screeningMicroarrayProbe discoverySmall molecules

More Related Videos

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
08:49

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

Published on: June 20, 2025

1.2K
Author Spotlight: Unraveling Vitamin A Transport Mechanisms — Linking Liver Receptors to Vision Health Through RBPR2 and RBP4 Interactions
08:18

Author Spotlight: Unraveling Vitamin A Transport Mechanisms — Linking Liver Receptors to Vision Health Through RBPR2 and RBP4 Interactions

Published on: October 4, 2024

1.5K

Related Experiment Videos

Last Updated: Feb 3, 2026

Ligand Nano-cluster Arrays in a Supported Lipid Bilayer
10:34

Ligand Nano-cluster Arrays in a Supported Lipid Bilayer

Published on: April 23, 2017

7.3K
Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
08:49

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

Published on: June 20, 2025

1.2K
Author Spotlight: Unraveling Vitamin A Transport Mechanisms — Linking Liver Receptors to Vision Health Through RBPR2 and RBP4 Interactions
08:18

Author Spotlight: Unraveling Vitamin A Transport Mechanisms — Linking Liver Receptors to Vision Health Through RBPR2 and RBP4 Interactions

Published on: October 4, 2024

1.5K

Area of Science:

  • Drug discovery and development
  • Chemical biology
  • Protein engineering

Background:

  • Many therapeutic protein targets are considered "undruggable" due to lack of structural data or binding pockets.
  • Array-based methods like small-molecule microarray screening aid ligand discovery for challenging targets.
  • Screening short-lived proteins in relevant conformations using cell lysates is technically difficult.

Purpose of the Study:

  • To present a protocol for array-based screening of short-lived proteins.
  • To enable ligand discovery for previously undruggable therapeutic targets.
  • To overcome technical challenges in screening proteins with short half-lives.

Main Methods:

  • Leveraging in vitro translation strategies.
  • Array-based screening against large small-molecule libraries.
  • Application to short-lived proteins in physiologically relevant conformations.

Main Results:

  • Successful adaptation of array-based screening for short-lived proteins.
  • Facilitation of ligand discovery for challenging therapeutic targets.
  • Overcoming limitations of previous cell lysate-based array screening.

Conclusions:

  • The presented protocol enables ligand discovery for previously undruggable, short-lived protein targets.
  • In vitro translation combined with array-based screening is a powerful approach for challenging drug targets.
  • This method expands the scope of targets amenable to small-molecule drug discovery.