Parsimonious Charge Deconvolution for Native Mass Spectrometry

• DOI: 10.1021/acs.jproteome.7b00839
• Publication Date: 2018-01-29T14:10:51Z
• Authors: Marshall Bern; Tomislav Caval; Yong J. Kil; Wilfred Tang; Christopher Becker; Eric Carlson; Doron Kletter; K. Ilker Sen; Nicolas Galy; Dominique Hagemans; Vojtech Franc; Albert J. R. Heck
• Keywords: glycoprotein; 0301 basic medicine; Spectrometry, Mass, Electrospray Ionization; maximum entropy; Daclizumab; Glycosylation; Entropy; Static Electricity; Cetuximab; high-resolution native mass spectrometry; Antibodies, Monoclonal, Humanized; Peptide Mapping; parsimony; 03 medical and health sciences; cetuximab; Humans; Trypsin; intact mass; Glycoproteins; algorithm; Properdin; factor P; Infliximab; Peptide Fragments; Solutions; properdin; daclizumab; monoclonal antibody; Immunoglobulin G; Proteolysis; infliximab; Algorithms

Charge deconvolution infers the mass from over charge (m/z) measurements in electrospray ionization spectra. When applied a wide input m/z or broad target range, charge-deconvolution algorithms can produce artifacts, such as false masses at one-half one-third of correct mass. Indeed, maximum entropy term objective function MaxEnt, most commonly used algorithm, favors deconvolved spectrum with many peaks one fewer peaks. Here we describe new "parsimonious" algorithm that produces artifacts. The is especially well-suited to high-resolution native spectrometry intact glycoproteins and protein complexes. Deconvolution spectra poses special challenges due salt small molecule adducts, multimers, ranges, lower states. We demonstrate performance on range samples. On heavily glycosylated plasma properdin glycoprotein, could deconvolve monomer dimer simultaneously and, when focused monomer, gave accurate interpretable for glycoforms had previously been analyzed manually using rather than masses. therapeutic antibodies, facilitated analysis extensions, truncations, Fab glycosylation. facilitates use qualitative quantitative assemblies.