title: A computational model for protein ionization by electrospray based on gas-phase basicity.
abstract: 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.
authors.affiliation: SISSA and INFM-DEMOCRITOS Center, Trieste, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Marchese
authors.forename: Rita
authors.initials: R
authors.lastname: Grandori
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni
authors.forename: Simone
authors.initials: S
authors.lastname: Raugei
mesh_terms: D000818:Animals; D002417:Cattle; D005740:Gases / Q000737:chemistry*; D006801:Humans; D056004:Molecular Dynamics Simulation; D011506:Proteins / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D005740:Gases; D011506:Proteins