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Related Concept Videos

The Equilibrium Binding Constant and Binding Strength02:18

The Equilibrium Binding Constant and Binding Strength

The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
The Equilibrium Binding Constant and Binding Strength02:18

The Equilibrium Binding Constant and Binding Strength

The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
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...
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...

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Related Experiment Video

Updated: Jul 6, 2026

Fluorescence Anisotropy as a Tool to Study Protein-protein Interactions
10:44

Fluorescence Anisotropy as a Tool to Study Protein-protein Interactions

Published on: October 21, 2016

Ligand binding efficiency: trends, physical basis, and implications.

Charles H Reynolds1, Brett A Tounge, Scott D Bembenek

  • 1Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Welsh and McKean Roads, Spring House, Pennsylvania 19477, USA. creynol1@prdus.jnj.com

Journal of Medicinal Chemistry
|April 3, 2008
PubMed
Summary
This summary is machine-generated.

Smaller drug molecules generally show higher ligand efficiency, meaning better potency relative to size. This finding impacts drug discovery strategies, from screening to computational modeling.

Related Experiment Videos

Last Updated: Jul 6, 2026

Fluorescence Anisotropy as a Tool to Study Protein-protein Interactions
10:44

Fluorescence Anisotropy as a Tool to Study Protein-protein Interactions

Published on: October 21, 2016

Area of Science:

  • Drug discovery and medicinal chemistry
  • Computational chemistry
  • Biophysics

Background:

  • Ligand efficiency (potency/size) is a key metric in drug discovery.
  • Smaller ligands are generally associated with improved drug properties like bioavailability.
  • Understanding ligand size-potency relationships is crucial for optimizing drug candidates.

Purpose of the Study:

  • To investigate the relationship between ligand size and ligand efficiency across diverse targets.
  • To identify the underlying causes of observed size-dependent trends in ligand efficiency.
  • To assess the implications of these findings for various drug discovery methodologies.

Main Methods:

  • Analysis of thousands of ligand datasets across multiple biological targets.
  • Statistical evaluation of ligand efficiency as a function of molecular size.
  • Development of hypotheses to explain the observed size dependence.

Main Results:

  • Ligand efficiency is demonstrably dependent on ligand size.
  • Smaller ligands exhibit higher average ligand efficiencies compared to larger ligands.
  • Two primary factors contribute: reduced fit quality with increasing size and decreased per-atom accessible surface area.

Conclusions:

  • Ligand size is a critical determinant of ligand efficiency.
  • The findings necessitate re-evaluation of high-throughput screening hit analysis and fragment-based drug discovery approaches.
  • Computational models predicting potency should incorporate ligand size effects.