Prediction of collision-induced-dissociation spectra of peptides with post-translational or process-induced modifications.

Mass spectrometry, combined with collision-induced dissociation (CID), has become the method of choice for analyzing protein post-translational and process-induced modifications. However, confident and automated identification of modifications and modification sites is often challenged by the diversity of modifications and their labile nature under typical CID conditions. An accurate prediction of the CID spectra of modified peptides will improve the reliability of automated determination of modifications and modification sites. In this article, the kinetic model for the prediction of peptide CID spectra is extended to the prediction of the CID spectra of modified peptides. The mathematical model for predicting CID spectra of peptides with enzymatic and chemical modifications such as (1) phosphorylation of serine, threonine, and tyrosine, (2) S-carboxymethylation and carbamidomethylation of cysteine, (3) different stages of oxidation of methionine, tryptophan, and cysteine, (4) glycation of lysine, (5) O-mannosylation of serine, (6) hydroxylation of lysine, and (7) N-monomethylation and N-dimethylation of lysine is described. The mathematical model, once established with CID spectra of peptides with known modifications and modification sites, is able to predict CID spectra with excellent accuracy in ion intensities, facilitating more reliable identification of modification and modification sites.