Protein State‐Dependent Chemical Biology

Chemical methods that provide a readout of biochemical changes within a cell at the protein level enable precise characterization of biological phenotypes that may not always be encoded in the genome or inferred from the transcriptome. Post‐translational regulation of protein activity differs from genetic and transcriptional as it usually occurs on a timescale of seconds to minutes rather than hours and days. This regulation is associated with dynamic changes in protein landscapes as a direct result of protein conformational changes induced by post‐translational modifications of critical amino acid residues, protein translocations, and changes in protein interactomes. Herein, we reflect on current broad‐scale mass spectrometry‐enabled chemical biology methods used to interrogate different protein states and dynamic protein landscapes and provide an outlook on the field of state‐dependent chemical biology.