Structure-based drug discovery (SBDD) is an indispensable approach for the design and optimization of new therapeutic agents. Here, we highlight the rapid progress that has turned cryo‐electron microscopy (cryoEM) into an exceptional SBDD tool, and the wealth of new structural information it is providing for high-value pharmacological targets. We review key advantages of a technique that directly images vitrified biomolecules without the need for crystallization; both in terms of a broader array of systems that can be studied and the different forms of information it can provide, including heterogeneity and dynamics. We discuss near- and far-future developments, working in concert towards achieving the resolution and throughput necessary for cryoEM to make a widespread impact on the SBDD pipeline.

基于结构的药物发现 (SBDD) 是设计和优化新治疗药物不可或缺的方法。在这里，我们强调了将冷冻电子显微镜 (cryoEM) 转变为卓越的 SBDD 工具的快速进展，以及它为高价值药理学靶点提供的大量新结构信息。我们回顾了直接成像玻璃化生物分子而不需要结晶的技术的主要优点；既可以研究更广泛的系统，也可以提供不同形式的信息，包括异质性和动态性。我们讨论近期和远期的发展，共同努力实现 cryoEM 对 SBDD 管道产生广泛影响所需的分辨率和吞吐量。