This chapter highlights many of the fundamental concepts and technologies in the field of top-down mass spectrometry (TDMS), and provides numerous examples of contributions that TD is making in biology, biophysics, and clinical investigations. TD workflows include variegated steps that may include non-specific or targeted preparative strategies, orthogonal liquid chromatography techniques, analyte ionization, mass analysis, tandem mass spectrometry (MS/MS) and informatics procedures. This diversity of experimental designs has evolved to manage the large dynamic range of protein expression and diverse physiochemical properties of proteins in proteome investigations, tackle proteoform microheterogeneity, as well as determine structure and composition of gas-phase proteins and protein assemblies.
Keywords: Alternative splicing; Bottom-up; Charge reduction; Chromatography; Data-dependent; Data-independent; Electrospray ionization; FT-ICR; Fourier transform; Hydrogen/deuterium exchange; Informatics; Label-free quantitation; Mass spectrometry; Membrane proteins; Native MS; Orbitrap; Post-translational modifications; Protein; Proteoform; Proteomics; Quadrupole ion trap; Reversed-phase; Review; SILAC; SNPs; Supercharging; Tandem MS; Time-of-flight; Top-down.