Abstract
Determining the total number of charged residues corresponding to a given value of net charge for peptides and proteins in gas phase is crucial for the interpretation of mass-spectrometry data, yet it is far from being understood. Here we show that a novel computational protocol based on force field and massive density functional calculations is able to reproduce the experimental facets of well investigated systems, such as angiotensin II, bradykinin, and tryptophan-cage. The protocol takes into account all of the possible protomers compatible with a given charge state. Our calculations predict that the low charge states are zwitterions, because the stabilization due to intramolecular hydrogen bonding and salt-bridges can compensate for the thermodynamic penalty deriving from deprotonation of acid residues. In contrast, high charge states may or may not be zwitterions because internal solvation might not compensate for the energy cost of charge separation.
Highlights
Predicting the structural properties of proteins in the gas phase is crucial to interpret mass spectrometry data, yet this is far from being understood [1,2,3,4,5,6,7,8,9,10]
In the last two decades mass spectrometry has given an impressive contribution to biochemistry, protein science, proteomics and structural biology
Results suggest that internal solvation can stabilize charge separation with the formation of zwitterionic states
Summary
Predicting the structural properties of proteins in the gas phase is crucial to interpret mass spectrometry data, yet this is far from being understood [1,2,3,4,5,6,7,8,9,10]. The key issue of the charge state of ionizable groups, presumably different from that in solution, is even less clear [2,51,52,53]. The number of ionized groups is generally assumed to be equal to the net charge of the protein ion [54,55,56]. Electrostatic energy calculations based on this supposition fail to reproduce experimental values of apparent gas-phase basicity (GPB) for folded protein ions [57]. The GPB of a basic species B is defined as the negative of the free-energy change, DG, for the gas-phase protonation reaction
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