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

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...
Ligand Binding Sites02:40

Ligand Binding Sites

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...
Drug-Receptor Bonds01:25

Drug-Receptor Bonds

Drug-receptor bonds are formed through various chemical forces when drugs interact with target cells. Covalent bonds, strong and irreversible, are exemplified by DNA-alkylating anticancer agents that inhibit cell division. However, such irreversible drug binding lacks selectivity and can modify the DNA of the surrounding healthy cells. Covalent binding often contributes to tissue toxicity, as seen with chloroform and paracetamol metabolites binding to the liver, causing hepatotoxicity.
In...
Dose-Response Relationship: Selectivity and Specificity01:25

Dose-Response Relationship: Selectivity and Specificity

Drugs exert their therapeutic effects by interacting with receptors, enzymes, or ion channels that are present throughout the human body. The strength and duration of the interaction between a drug and its target receptor are characterized by the selectivity and specificity of the drug. Selectivity refers to a drug's strong preference for its intended target over other targets. For instance, isoprenaline, a non-selective β-adrenergic agonist, interacts with both β1- and β2-adrenergic receptors...
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

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 the...
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

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 the...

You might also read

Related Articles

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

Sort by
Same author

The divergent LARP1 PAM2 motif adopts a non-canonical conformation for MLLE binding.

Biochemical and biophysical research communications·2026
Same author

The cytoplasmic domains of the CNNM family of transmembrane proteins modulate the ion channel-kinase TRPM7.

The Journal of biological chemistry·2025
Same author

Solution-based studies on the contact between the complement receptor 3 ligand-binding domain and simvastatin.

Biochimica et biophysica acta. Proteins and proteomics·2025
Same author

Discovery of KDX1381, a Bivalent CK2α Inhibitor for the Treatment of Solid Tumors as a Single Agent or in Combination.

Journal of medicinal chemistry·2025
Same author

Picomolar bivalent inhibitors of protein kinase CK2 active against β-coronavirus replication.

European journal of medicinal chemistry·2025
Same author

Rational Design and Synthesis of Highly Stable Haloflavanone DNA Methyltransferase Inhibitors Inducing Tumor Suppressor Gene Re-expression in Cancer Cells.

Journal of medicinal chemistry·2025

Related Experiment Video

Updated: Jun 12, 2026

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery
06:26

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery

Published on: May 16, 2021

Ligand specificity in fragment-based drug design.

Sarah Barelier1, Julien Pons, Kalle Gehring

  • 1Laboratoire des Sciences Analytiques, UMR CNRS 5180, Universite de Lyon, Universite Claude Bernard, Lyon 1, Bat. ESCPE Lyon, Domaine Scientifique de la Doua, 69100 Villeurbanne, France.

Journal of Medicinal Chemistry
|June 26, 2010
PubMed
Summary

Fragment-based drug design uses small molecules to find binding sites on proteins. Researchers found that fragment binders are versatile, with some scaffolds showing broad applicability across diverse protein targets.

More Related Videos

NMR-Based Fragment Screening in a Minimum Sample but Maximum Automation Mode
09:19

NMR-Based Fragment Screening in a Minimum Sample but Maximum Automation Mode

Published on: June 4, 2021

Workflow and Tools for Crystallographic Fragment Screening at the Helmholtz-Zentrum Berlin
06:29

Workflow and Tools for Crystallographic Fragment Screening at the Helmholtz-Zentrum Berlin

Published on: March 3, 2021

Related Experiment Videos

Last Updated: Jun 12, 2026

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery
06:26

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery

Published on: May 16, 2021

NMR-Based Fragment Screening in a Minimum Sample but Maximum Automation Mode
09:19

NMR-Based Fragment Screening in a Minimum Sample but Maximum Automation Mode

Published on: June 4, 2021

Workflow and Tools for Crystallographic Fragment Screening at the Helmholtz-Zentrum Berlin
06:29

Workflow and Tools for Crystallographic Fragment Screening at the Helmholtz-Zentrum Berlin

Published on: March 3, 2021

Area of Science:

  • Biochemistry
  • Structural Biology
  • Drug Discovery

Background:

  • Fragment-based drug design (FBDD) identifies low-molecular weight compounds for potent inhibitor development.
  • The specificity of low-complexity, low-affinity FBDD molecules is under-explored.
  • Understanding fragment binding is crucial for optimizing drug development strategies.

Purpose of the Study:

  • To investigate the binding specificity of small molecule fragments across diverse protein targets.
  • To identify versatile fragment scaffolds and assess their applicability in drug design.
  • To explore the relationship between protein druggability and fragment binding specificity.

Main Methods:

  • Nuclear Magnetic Resonance (NMR) spectroscopy was employed to study fragment-protein interactions.
  • 150 diverse fragments were screened against five target proteins.
  • Target proteins included Bcl-2 family members (Bcl-x(L), Bcl-w, Mcl-1), human peroxiredoxin 5, and human serum albumin.

Main Results:

  • Fragments demonstrated versatile binding capabilities, identifying 'hot spots' across different protein targets.
  • Two fragment scaffolds emerged as preferred binders irrespective of the protein target.
  • Binding specificity varied; low specificity was noted for homologous or poorly druggable proteins, while higher specificity was observed for highly druggable targets.

Conclusions:

  • Fragment binders are adaptable and can identify key binding sites on various macromolecules.
  • Certain fragment scaffolds exhibit broad utility, suggesting potential for universal application in FBDD.
  • Achieving high specificity in fragment-based drug design is influenced by protein target characteristics and druggability.