Use of mass spectrometric molecular weight information to identify proteins in sequence databases

During the last decade new ionization techniques have made it possible to measure the molecular weight of many intact proteins by mass spectrometry, and they have made it much easier to obtain a mass spectrometric peptide map of a protein. At the same time advances in protein and DNA sequencing technology are resulting in an exponential increase in the number of sequences deposited in databases. Here we investigate the possibility to use mass spectrometric data to identify proteins in databases. Searching a database by total molecular weight is found to be an easy and sometimes sufficient approach. For more specificity and for error tolerance in both the mass spectrometric data and the database information we search by partial mass spectrometric peptide map of the protein. In general, just four to six proteolytic peptides measured with a mass accuracy between 0.1 and 0.01% allow a useful search of databases such as the Protein Identification Resource (PIR). As the size of DNA and protein sequence databases grows, protein identification by partial mass spectrometric peptide maps should become increasingly powerful and may become a general method to identify and characterize proteins.