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High-Throughput Native Mass Spectrometry Screening in Drug Discovery
Agni F M Gavriilidou1, Kleitos Sokratous1, Hsin-Yung Yen1
1OMass Therapeutics, Oxford, United Kingdom.
Frontiers in Molecular Biosciences
|May 2, 2022
Summary
Native mass spectrometry (MS) offers insights into dynamic protein-ligand interactions crucial for therapeutic molecule design. This versatile technique complements traditional methods, enhancing drug discovery pipelines.
Area of Science:
- Biophysics
- Biochemistry
- Drug Discovery
Background:
- Protein-ligand interactions are key to designing new therapeutics.
- Studying these complexes requires biophysical methods post-purification.
- Established techniques include ITC, SPR, NMR, crystallography, and cryo-EM.
Purpose of the Study:
- To discuss the principles and applications of native mass spectrometry (MS).
- To highlight native MS's role in studying dynamic protein-ligand complexes.
- To explore native MS integration into drug discovery pipelines.
Main Methods:
- Native mass spectrometry (MS) for studying proteins and their assemblies.
- Complementary biophysical techniques (ITC, SPR, NMR, crystallography, cryo-EM).
Main Results:
- Native MS provides data on binding thermodynamics and stoichiometry.
- It offers insights into ternary and quaternary protein structures.
- Native MS is a versatile tool for dynamic, heterogeneous systems.
Conclusions:
- Native MS is a valuable addition to the drug discovery toolkit.
- It complements existing methods for studying protein-ligand interactions.
- Future developments promise further advancements in therapeutic molecule design.
