A Computational Model for Protein Ionization by Electrospray Based on Gas-Phase Basicity

作者：Marchese Roberto; Grandori Rita^*; Carloni Paolo; Raugei Simone

来源：Journal of the American Society for Mass Spectrometry, 2012, 23(11): 1903-1910.

DOI：10.1007/s13361-012-0449-0

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

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.

• 出版日期2012-11