Mechanisms of Fragmentation of Post Translationally Modified Peptides
EMSL Project ID
13301
Abstract
It has recently been demonstrated using a collision-induced dissociation (CID) quadrupole ion trap mass spectrometer that under similar conditions to those where enhanced C-terminal aspartic acid cleavage is commonly observed, the diagnostic neutral loss of CH3SOH (64 Da) from the side chain of peptide ions containing methionine sulfoxide, a common post translational modification, is the dominant fragmentation process [2]. This fragmentation occurs for model compounds as well as from a “real world” database of MS/MS spectra of tryptic peptides. Using SID FT-ICR MS and RRKM methods, we proposed to examine the dissociation reactions of a set of protonated peptides containing oxidized methionine, as well as those containing both oxidized methionine and aspartic acid. The aim is to obtain further insights into the energetics and dynamics of these competing fragmentation processes. The synthetic peptides to be studied have the common structure of GAILXGAILY (where X=D, M, or M(ox) (M(ox) represents methionine sulfoxide residue) and Y=K or R), some of which have previously been studied using CID in an ion trap mass spectrometer [2]. This choice of peptides, therefore, allows a direct comparison and contrast of the fragmentation processes of model “tryptic” peptides under two different mass spectrometric conditions. Since charge directed and charge remote mechanisms for loss of CH3SOH can both operate [2,3], the influence of proton affinity of the C-terminal amino acid of these “tryptic” peptides will also to be explored in order to determine how this effects fragmentation within the mobile proton model.
Molecular mechanics modeling and structure optimization at the semi-empirical theory available from PNNL Advanced Computing Facilities, the Molecular Science Computing Facility (MSCF), will be used to perform comprehensive conformational search and to determine the vibrational frequencies of the series of protonated peptides. We will use stimulated annealing to explore the conformational space. Lowest energy structures obtained from molecular mechanics modeling will be further optimized using AM1 calculations. The results will provide an important insight on the influence of the secondary structure of a peptide on its fragmentation behavior observed experimentally. In addition, vibrational frequencies are essential for conducting RRKM modeling of experimental data
Project Details
Start Date
2005-03-01
End Date
2007-03-19
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
H. Lioe, J. Laskin, G. E. Reid, and R. A. J. O’Hair “Energetics and Dynamics of Fragmentation of Protonated Peptides containing a Methionine Sulfoxide or an Aspartic Acid Residue via Energy- and Time-Resolved Surface Induced Dissociation Study”, J. Phys. Chem. A, 111, 10580-10588 (2007)