A computational model for protein ionization by electrospray based on gas-phase basicity

Roberto Marchese, Rita Grandori, Paolo Carloni, Simone Raugei

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


Identifying the key factor(s) governing the overall protein charge is crucial for the interpretation of electrospray-ionization mass spectrometry data. Current hypotheses invoke different principles for folded and unfolded proteins. Here, first we investigate the gas-phase structure and energetics of several proteins of variable size and different folds. The conformer and protomer space of these proteins ions is explored exhaustively by hybrid Monte-Carlo/molecular dynamics calculations, allowing for zwitterionic states. From these calculations, the apparent gas-phase basicity of desolvated protein ions turns out to be the unifying trait dictating protein ionization by electrospray. Next, we develop a simple, general, adjustable-parameter-free model for the potential energy function of proteins. The model is capable to predict with remarkable accuracy the experimental charge of folded proteins and its well-known correlation with the square root of protein mass.

Original languageEnglish
Pages (from-to)1903-1910
Number of pages8
JournalJournal of the American Society for Mass Spectrometry
Issue number11
Publication statusPublished - Nov 2012


  • Density functional theory calculations
  • Electrospray ionization
  • Gas-phase basicity
  • Molecular-dynamics
  • Monte-Carlo sampling
  • Protein ionization
  • Simulations

ASJC Scopus subject areas

  • Structural Biology
  • Spectroscopy

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