Discovering the landscape of protein modifications

Protein modifications modulate nearly every aspect of cell biology in organisms, ranging from Archaea to Eukaryotes. The earliest evidence of covalent protein modifications was found in the early 20th century by studying the amino acid composition of proteins by chemical hydrolysis. These discoveries challenged what defined a canonical amino acid. The advent and rapid adoption of mass-spectrometry-based proteomics in the latter part of the 20th century enabled a veritable explosion in the number of known protein modifications, with more than 500 discrete modifications counted today. Now, new computational tools in data science, machine learning, and artificial intelligence are poised to allow researchers to make significant progress in discovering new protein modifications and determining their function. In this review, we take an opportunity to revisit the historical discovery of key post-translational modifications, quantify the current landscape of covalent protein adducts, and assess the role that new computational tools will play in the future of this field.

Automated summary

Protein modifications play a significant role in cell biology across various organisms. Discoveries in the early 20th century challenged traditional definitions of amino acids, and the advent of mass-spectrometry-based proteomics in the latter part led to a rapid increase in known protein modifications, with over 500 identified today. New computational tools in data science, machine learning, and artificial intelligence are expected to further advance the discovery and understanding of protein modifications in the future.