Leveraging Advances in Cryo Electron Microscopy to Facilitate Drug Discovery

Getting a new therapeutic to market can take years and millions of dollars in funding for research and development, clinical trials, and drug production. Structure based drug design is a helpful tool in the pre-clinical research and development process to improve drug candidates. Cryo-EM is increasingly utilized among a suite of structural biology techniques to elucidate structures of target proteins in complex with therapeutic drugs and antibodies. However, challenges to determining cryo-EM structures of therapeutic targets remain including sample size limitations and preferred orientation. Here we discuss a variety of issues encountered in cryo-EM structure determination with three case studies, highlighting how overcoming challenges facilitates moving drug discovery forward.