Variable modifications are those that are not necessarily found on every example of that amino acid in the proteome. Searching for variable mods increases the size of the database because a different theoretical spectrum needs to be generated for modified and unmodified versions of each peptide that could be modified. By contrast fixed modifications are found on every example of a particular amino acid. This doesn't change the size of the database because there is only one version of that amino acid so only one theoretical spectrum needs to be made. The most common fixed mod is carbamidomethylated cystine. This is the result of using alkylating agents on your sample to prevent the formation of disulfide bonds which would mess up the measurements.
Variable modifications are those that are not necessarily found on every example of that amino acid in the proteome. Searching for variable mods increases the size of the database because a different theoretical spectrum needs to be generated for modified and unmodified versions of each peptide that could be modified. By contrast fixed modifications are found on every example of a particular amino acid. This doesn't change the size of the database because there is only one version of that amino acid so only one theoretical spectrum needs to be made. The most common fixed mod is carbamidomethylated cystine. This is the result of using alkylating agents on your sample to prevent the formation of disulfide bonds which would mess up the measurements.More
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