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Ligand Binding Sites

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...

The Equilibrium Binding Constant and Binding Strength

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 and Linkage

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...

Conserved Binding Sites

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...

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Related Experiment Video

Updated: Sep 15, 2025

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

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

Published on: June 4, 2021

Exploring the Ligandability of 53BP1 through Fragment-Based Approaches.

Beatrice Chiew¹, Menachem J Gunzburg^1,2, Caroline A Foley^2,3

¹Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.

ACS Medicinal Chemistry Letters

|July 16, 2025

Summary

Researchers identified compounds targeting the 53BP1 protein, a key player in DNA repair. This discovery offers potential therapeutic strategies for cancers linked to BRCA-1 mutations by developing 53BP1 antagonists.

Keywords:

53BP1 chemoinformatics epigenetics fragment screening fragment-based drug design nuclear magnetic resonance surface plasmon resonance

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Last Updated: Sep 15, 2025

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

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

Published on: June 4, 2021

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

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Published on: May 16, 2021

Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source

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Published on: May 29, 2021

Area of Science:

Biochemistry and Molecular Biology
Cancer Research
Drug Discovery

Background:

53BP1 is a crucial DNA damage response protein.
BRCA-1 mutations are linked to breast and ovarian cancers.
53BP1 antagonists may counteract BRCA-1 mutation effects.

Purpose of the Study:

Identify compounds binding to the 53BP1 Tudor domain.
Develop structure-activity relationships for 53BP1 binders.
Explore 53BP1 as a therapeutic target for cancer.

Main Methods:

Fragment screening to identify initial binders.
Chemoinformatic workflow for analogue selection.
Structure-activity relationship (SAR) analysis.

Main Results:

Identified fragment compounds that bind to the 53BP1 Tudor domain.
Developed near-neighbor analogues with improved binding affinity.
Established SAR for the identified compound series.

Conclusions:

The identified compounds are promising starting points for 53BP1 antagonist development.
This approach is effective for discovering hits against methyl-lysine reader proteins.
Targeting 53BP1 offers a potential therapeutic avenue for BRCA-1-associated cancers.