When there are a couple of PTMs of interest, it is recommended to choose up to about 5 PTMs in a standard sequence database search. When a more explorative approach is preferred, one could consider using open modification searching, an unbiased approach for investigating PTMs . In standard database searching an observed spectrum is not scored against the complete database, instead, only a subset of the peptides are scored, namely those whose mass is within a narrow tolerance window of the observed precursor mass. When this is extended to a larger window, a so-called open search is performed in which a modified peptide can be matched to its unmodified counterpart, enabling the identification of any PTM within the mass window.