Accelerating Structure Based Drug Design for Challenging Proteins by CryoEM

For decades now, X-ray crystallography has been the go-to technique to unravel structural details of proteins, in pursuit of answering various biological questions and aiding structure based drug design. However, in the last few years, cryo-Electron Microscopy (cryoEM) has garnered a lot of attention and is quickly advancing towards being the most effective and powerful macromolecular structure determination tool due its ability to the otherwise challenging samples such as large protein complexes, flexible proteins with multiple conformations, viruses, and membrane proteins. Various technological advancements in the last decade with respect to detector quality, detector speed, data collection and processing speed, automation in software, improvements in sample preparation, footprint of the microscope, and more affordability has also enabled many large pharmaceuticals and smaller biotechs taking up cryoEM as the first choice tool for structure determination. The scientific community marveled at the recent Nature article that reported a 1.2A cryoEM structure of apoferritin, clearly showing not just water molecules, but other polar and nonpolar hydrogens as well. With this resolution revolution, cryoEM has opened the doors to a lot more research projects which have been trying X-ray crystallography without much success. Here we are presenting a few recently published high resolution cryoEM structures including those of SARS-CoV2, how this tool has been advancing in the last few years, how the new breakthroughs have brought about a resolution revolution once again, and how we are democratizing cryoEM by bringing it to the masses.