The recent revolution in cryo-EM has produced an explosion of structures at near-atomic or better resolution. This has allowed cryo-EM structures to provide visualization of bound small-molecule ligands in the macromolecules, and these new structures have provided unprecedented insights into the molecular mechanisms of complex biochemical processes. They have also had a profound impact on drug discovery, defining the binding modes and mechanisms of action of well-known drugs as well as driving the design and development of new compounds. This review will summarize and highlight some of these structures. Most excitingly, the latest cryo-EM technology has produced structures at 1.2 Å resolution, further solidifying cryo-EM as a powerful tool for drug discovery. Therefore, cryo-EM will play an ever-increasing role in drug discovery in the coming years.

最近的低温 EM 革命已经产生了近原子或更高分辨率的结构爆炸。这使得低温 EM 结构能够提供大分子中结合的小分子配体的可视化，并且这些新结构为复杂生化过程的分子机制提供了前所未有的见解。它们还对药物发现产生了深远影响，定义了知名药物的结合模式和作用机制，并推动了新化合物的设计和开发。本综述将总结并强调其中的一些结构。最令人兴奋的是，最新的冷冻电镜技术已经产生了 1.2 Å 分辨率的结构，进一步巩固了冷冻电镜作为药物发现的强大工具的地位。所以，