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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...
Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses 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...
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:

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Related Experiment Video

Updated: May 14, 2026

Modeling Ligands into Maps Derived from Electron Cryomicroscopy
09:30

Modeling Ligands into Maps Derived from Electron Cryomicroscopy

Published on: July 19, 2024

Ligand binding site identification by higher dimension molecular dynamics.

Achani K Yatawara1, Milan Hodoscek, Dale F Mierke

  • 1Department of Chemistry, Dartmouth College , Hanover, New Hampshire 03755, United States.

Journal of Chemical Information and Modeling
|February 12, 2013
PubMed
Summary

We developed a novel four-dimensional (4D) molecular dynamics (MD) protocol for efficient binding site identification. This method accurately predicts ligand binding pockets in proteins, aiding drug discovery.

Related Experiment Videos

Last Updated: May 14, 2026

Modeling Ligands into Maps Derived from Electron Cryomicroscopy
09:30

Modeling Ligands into Maps Derived from Electron Cryomicroscopy

Published on: July 19, 2024

Area of Science:

  • Computational chemistry
  • Structural biology
  • Drug discovery

Background:

  • Identifying ligand binding sites is crucial for understanding protein function and designing drugs.
  • Traditional methods can be computationally expensive and require prior knowledge of binding site locations.

Purpose of the Study:

  • To introduce a new four-dimensional (4D) molecular dynamics (MD) protocol for unbiased identification of guest-host binding sites.
  • To demonstrate the protocol's efficacy on diverse protein targets with varying binding pocket characteristics and ligand affinities.

Main Methods:

  • A novel 4D molecular dynamics (MD) protocol was employed, representing ligands in four spatial dimensions for enhanced sampling.
  • The method was tested on the Abl kinase domain (deep pocket, high affinity) and the PDZ1 domain of PSD-95 (shallow pocket, micromolar affinity).
  • Ligands were initially placed at the protein's center, away from known binding sites, to ensure unbiased exploration.

Main Results:

  • The 4D MD protocol successfully identified the known binding sites for both the Abl kinase domain and the PDZ1 domain.
  • The method demonstrated efficiency in sampling and overcoming energy barriers to locate the lowest energy binding pockets.
  • Accurate docking into experimentally validated binding sites was achieved for both model systems.

Conclusions:

  • The proposed 4D MD protocol offers a rapid and efficient approach for identifying protein binding sites.
  • This method can aid in the discovery of novel binding pockets without requiring a priori knowledge of their location.
  • The protocol shows promise for advancing drug discovery and understanding molecular interactions.