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Updated: Mar 16, 2026
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NMR-Based Fragment Screening in a Minimum Sample but Maximum Automation Mode
Published on: June 4, 2021
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Native Mass Spectrometry in Fragment-Based Drug Discovery
Liliana Pedro1, Ronald J Quinn2
1Eskitis Institute for Drug Discovery, Griffith University, Brisbane 4111, Queensland, Australia. liliana.pedro@griffithuni.edu.au.
Molecules (Basel, Switzerland)
|August 3, 2016
Summary
Native mass spectrometry (MS) directly analyzes protein-ligand interactions for fragment-based drug discovery (FBDD). This sensitive technique determines binding affinities, stoichiometry, and binding sites, accelerating drug development.
Area of Science:
- Biochemistry
- Analytical Chemistry
- Pharmacology
Background:
- Native mass spectrometry (MS) emerged in 1990, revolutionizing the analysis of noncovalent protein-ligand complexes.
- It has evolved into a rapid, sensitive, and automatable method crucial for modern research.
Purpose of the Study:
- To review the key attributes of native MS for fragment-based drug discovery (FBDD) campaigns.
- To highlight the utility of native MS in characterizing protein-ligand interactions.
Main Methods:
- Direct detection of weak ligand binding to proteins using native MS.
- Determination of stoichiometry, binding affinities (relative or absolute), and specificities.
- Elucidation of ligand-binding sites and mechanisms of cooperativity.
Main Results:
- Native MS directly detects and quantifies weak interactions in protein-ligand complexes.
- The technique provides insights into binding stoichiometry, affinity, and specificity.
- It enables detailed studies of binding thermodynamics and site identification.
Conclusions:
- Native MS is a powerful and versatile tool for fragment-based drug discovery.
- Its capabilities in analyzing noncovalent complexes significantly advance drug development pipelines.
- The review underscores the established utility and ongoing importance of native MS in FBDD.
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