Mark Schreuder, Mark Larance
Post-translational modifications (PTMs) can play vital roles in the protein's structure, function, localization, and interactions, enabling dynamic control of cellular processes. As such, understanding these modifications is essential to elucidate key biological mechanisms. This chapter discusses an unbiased, mass spectrometry-based approach using wildcard (open) searches in the Byonic platform to detect and identify nondisulfide cysteine PTMs. By targeting individual cysteines and scanning for mass shifts across a broad range, this strategy enables discovery of novel or unexpected modifications. The method is applicable to both new and existing datasets and can be extended to any amino acid, offering a versatile tool for redox and PTM-focused proteomics.