Thermo Fisher Scientific, Achtseweg Noord 5, 5651 GG Eindhoven, The Netherlands.
Thermo Fisher Scientific, Achtseweg Noord 5, 5651 GG Eindhoven, The Netherlands.
Drug Discov Today Technol. 2020 Dec;38:91-102. doi: 10.1016/j.ddtec.2020.12.003. Epub 2021 Jan 11.
Since the early 2010s, cryo-electron microscopy (cryo-EM) has evolved to a mainstream structural biology method in what has been dubbed the "resolution revolution". Pharma companies also began to use cryo-EM in drug discovery, evidenced by a growing number of industry publications. Hitherto limited in resolution, throughput and attainable molecular weight, cryo-EM is rapidly overcoming its main limitations for more widespread use through a new wave of technological advances. This review discusses how cryo-EM has already impacted drug discovery, and how the state-of-the-art is poised to further revolutionize its application to previously intractable proteins as well as new use cases.
自 21 世纪 10 年代初以来,冷冻电子显微镜(cryo-EM)已经发展成为一种主流的结构生物学方法,这被称为“分辨率革命”。制药公司也开始在药物发现中使用 cryo-EM,这一点可以从越来越多的行业出版物中得到证明。迄今为止,cryo-EM 在分辨率、通量和可达到的分子量方面受到限制,但通过新一轮技术进步,它正在迅速克服其广泛应用的主要限制。本文讨论了 cryo-EM 如何已经影响药物发现,以及最先进的技术如何进一步将其应用于以前难以处理的蛋白质以及新的用例中进行革命化。