If there are any phosphorylated peptides in my samples I would like to know. Why shouldn I always allow for phosphorylation in my searches?
Searching allowing for variable modifications increases the size of the database in silico making it more difficult to get confident answers. Modifications that only occur on the protein N-terminus such as protein N-terminal acetylation, or modifications that occur to fairly rare amino acids such as methionine oxidation, do not have a big impact, but searching for phosphorylation of serines and threonines, two common amino acids drastically increases the number of sequences being searched, will slow down your search and will give you less confident results.
