Ab initio and MS/MS studies on protonated peptides containing basic and acidic amino acid residues - I. Solvated proton vs. salt-bridged structures and the cleavage of the terminal amide bond of protonated RD-NH2

Béla Paizs, Sándor Suhai, Balázs Hargittai, Victor J. Hruby, Árpád Somogyi

Research output: Contribution to journalArticle

48 Scopus citations


The results of a detailed ab initio investigation on one of the simplest model peptides, RD-NH2, containing both basic (R) and acidic (D) residues are presented here. The ab initio (B3LYP/6-31+G(d,p)) relative energies of several internally solvated (IS) and salt-bridged (SB) structures are in the range of 0-33kcal/mol. Upon ion activation in a tandem mass spectrometer, the conversion of IS into SB structures is energetically feasible but very probably kinetically controlled. Several theoretical pathways are suggested for the NH3 loss from the amide terminus of protonated RD-NH2. The loss of NH3 is proposed to occur either via "four-center-one-step" (FCOS) processes or an "oxazolone ring" formation (OX). The FCOS pathways indicate that the formation of a SB structure is not a prerequisite for the loss of NH3 from the amide terminus. The ab initio results clearly show the complexity of the potential energy surface of even such a small protonated peptide that is manifested in different protonated structures and pathways for a "simple" NH3 loss. Low-energy CID MS2 and MS3 spectra of the singly charged RD-NH2 have also been recorded and discussed in conjunction with the theoretical results. A brief discussion on the limitations of our current model to the fragmentation behavior of larger peptides containing both basic and acidic amino acids is also presented.

Original languageEnglish (US)
Pages (from-to)203-232
Number of pages30
JournalInternational Journal of Mass Spectrometry
Issue number1
StatePublished - Aug 1 2002



  • Ab initio calculations
  • Cleavage of amide bond
  • Peptide fragmentation
  • Proton transfer
  • Tandem mass spectrometry

ASJC Scopus subject areas

  • Instrumentation
  • Condensed Matter Physics
  • Spectroscopy
  • Physical and Theoretical Chemistry

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