Dynamics of Proton Transfer and Cyclization of Protonated Peptides and Their Fragments in the Gas Phase

Gas-phase dissociations of protonated peptides in mass spectrometers are being widely applied for microsequencing in proteomics for protein identification, for de novo sequencing, and for determination of posttranslational modification sites, which are of great importance for deciphering genetic codes in the nature. Large-scale analyzing the mass spectra of the protonated peptides are fully automated with bioinformatics searching algorithms by correlating the experimental spectra with the theoretical spectra of the peptides in standard protein databases. Generating the theoretical spectra relies on knowledge of the gas-phase ion chemistries. Therefore, better understanding of the underlying dissociation mechanisms, energetics, and kinetics are of fundamental importance for improving the efficiency and precision of the current database searching algorithms in order to reduce the rates of false-positive protein identifications. Our research program aims to develop a dynamics model to describe the chemistries of the peptide dissociations in the gas phase at finite temperatures. In this three-year funding cycle, the dynamics effects of the peptide chain lengths and the amino-acid side chains on the proton-transfer and cyclization reactions of the protonated peptides will be systematically examined by means of density functional theory based molecular dynamics simulations. These chemical processes play important roles in the formation of cyclic peptides, a structural rearrangement process that leads to the unpleasant loss of sequence information in the mass spectrometric data.