De Novo Sequencing Methods in Proteomics

The review describes methods of de novo sequencing of peptides by mass spectrometry. De novo methods utilize computational approaches to deduce the sequence or partial sequence of peptides directly from the experimental MS/MS spectra. The concepts behind a number of de novo sequencing methods are discussed. The other approach to identify peptides by tandem mass spectrometry is to match the fragment ions with virtual peptide ions generated from a genomic or protein database. De novo methods are essential to identify proteins when the genomes are not known but they are also extremely useful even when the genomes are known since they are not affected by errors in a search database. Another advantage of de novo methods is that the partial sequence can be used to search for posttranslation modifications or for the identification of mutations by homology based software.