Running a Cost-Effective Modern Cryo-EM Facility for SPA Analysis

Setting up a new cryo-EM facility to obtain high-resolution protein structures is becoming increasingly common in both academic scientific research and industry. Here we describe how a 200 kV microscope equipped with modern detector and energy filter is a necessary, sufficient, and cost-effective choice for most protein structure research purposes, and can usually lead to sub 3 Å resolution structures with small ligand or drug molecular densities apparent. With large data resource computational facilities and ancillary vitrification instruments, a single person can run a cryo-EM facility, which can gradually become a basic resource needed for essential scientific research and drug discovery. Here we describe all aspects of such a cryo-EM facility, from sample preparation, to microscope setup for screening, to data collection and structure solution. It is hoped cryo-EM users can systematically follow these steps to initiate their research. In addition, a summary of new technologies implemented in the above-mentioned steps is described, and it will help cryo-EM users to expand their knowledge of how to better use the microscope to promote their research.