PNNL

Abstract

In the last two years, due to advances in protein separation and mass spectrometry, top-down mass spectrometry moved from analyzing single proteins to analyzing complex samples and identifying hundreds and even thousands of proteins. However, computational tools for database search of top-down spectra against protein databases are still in infancy. We describe MS-Align+, a fast algorithm for top-down protein identification based on spectral alignment that enables searches for unexpected post-translational modifications (PTMs). We also propose a method for evaluating statistical significance of top-down protein identifications and further benchmark MS-Align+ along with PIITA, ProSightPTM and SEQUEST, which were previously used for top-down MS/MS database searches. We demonstrate that MS-Align+ and PIITA significantly increase the number of identified proteins as compared to ProSightPTM and SEQUEST.