Analyte

Operating system

Mass spectrometry

Nanotechnology

Chemistry

Fragmentation (computing)

Materials science

Computer science

Chromatography

Biomolecule

Biochemistry

Computational biology

Biology

Chemical Reviews

Native mass spectrometry (MS) involves the analysis and characterization of macromolecules, predominantly intact proteins and protein complexes, whereby as much as possible the native structural features of the analytes are retained. As such, native MS enables the study of secondary, tertiary, and even quaternary structure of proteins and other biomolecules. Native MS represents a relatively recent addition to the analytical toolbox of mass spectrometry and has over the past decade experienced immense growth, especially in enhancing sensitivity and resolving power but also in ease of use. With the advent of dedicated mass analyzers, sample preparation and separation approaches, targeted fragmentation techniques, and software solutions, the number of practitioners and novel applications has risen in both academia and industry. This review focuses on recent developments, particularly in high-resolution native MS, describing applications in the structural analysis of protein assemblies, proteoform profiling of─among others─biopharmaceuticals and plasma proteins, and quantitative and qualitative analysis of protein-ligand interactions, with the latter covering lipid, drug, and carbohydrate molecules, to name a few.

High-Resolution Native Mass Spectrometry