Protein structure must be studied in its native cellular environment, otherwise, we risk overlooking the molecular crowding effects that new mass spectrometry (MS) based structural methods reveal about protein architecture in intact cells and cell lysates. These methods, including thermal proteome profiling and chemical crosslinking, leverage the bottom-up proteomics workflow to provide structural information on hundreds of proteins across the proteome. The capacity of MS to report on thousands of peptides in a single experiment allows for proteome-wide structural biology.
One of these cellular-based methods, in-cell fast photochemical oxidation of proteins (IC-FPOP), is an example of hydroxyl radical protein footprinting (HRPF). HRPF utilizes hydroxyl radicals to oxidatively modify solvent accessible sites in proteins. In vitro applications of HRPF are steadily on the rise and have successfully identified protein interactions sites and conformation changes. The extension of HRPF for in cell analysis has required several optimizations. Initial studies point to the promise of IC-FPOP for structural biology. In this Clinical OMICs webinar, we will focus on the development of in-cell protein footprinting and its application in drug engagement studies.
A live Q&A session will follow the presentations, offering you a chance to pose questions to our expert panelists.