Applications and prospects of cryo-EM in drug discovery

Zhu, Kong-Fu1; Yuan, Chuang2; Du, Yong-Ming3; Sun, Kai-Lei4; Zhang, Xiao-Kang5,6,7; Vogel, Horst8; Jia, Xu-Dong9; Gao, Yuan-Zhu10; Zhang, Qin-Fen9; Wang, Da-Ping1,11; Zhang, Hua-Wei1,12

2023-03-06

10.1186/s40779-023-00446-y

Military Medical Research   Impact Factor & Quartile

2095-7467

2054-9369

Drug discovery is a crucial part of human healthcare and has dramatically benefited human lifespan and life quality in recent centuries, however, it is usually time- and effort-consuming. Structural biology has been demonstrated as a powerful tool to accelerate drug development. Among different techniques, cryo-electron microscopy (cryo-EM) is emerging as the mainstream of structure determination of biomacromolecules in the past decade and has received increasing attention from the pharmaceutical industry. Although cryo-EM still has limitations in resolution, speed and throughput, a growing number of innovative drugs are being developed with the help of cryo-EM. Here, we aim to provide an overview of how cryo-EM techniques are applied to facilitate drug discovery. The development and typical workflow of cryo-EM technique will be briefly introduced, followed by its specific applications in structure-based drug design, fragment-based drug discovery, proteolysis targeting chimeras, antibody drug development and drug repurposing. Besides cryo-EM, drug discovery innovation usually involves other state-of-the-art techniques such as artificial intelligence (AI), which is increasingly active in diverse areas. The combination of cryo-EM and AI provides an opportunity to minimize limitations of cryo-EM such as automation, throughput and interpretation of medium-resolution maps, and tends to be the new direction of future development of cryo-EM. The rapid development of cryo-EM will make it as an indispensable part of modern drug discovery.

Cryo-electron microscopy (cryo-EM) Drug discovery Structure-based drug design Fragment-based drug discovery Proteolysis targeting chimeras Drug repurposing Artificial intelligence (AI)

SCI

English

First ; Corresponding

General & Internal Medicine

Medicine, General & Internal

WOS:000943371600001

BMC

2-s2.0-85149589873

Web of Science

1.Southern Univ Sci & Technol, Dept Biomed Engn, Shenzhen 518055, Guangdong, Peoples R China
2.Peking Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China
3.St Jude Childrens Res Hosp, Dept Struct Biol, Memphis, TN 38105 USA
4.Chinese Univ Hong Kong, Fac Sci, Ctr Prot Sci & Crystallog, Sch Life Sci, Hong Kong 999077, Peoples R China
5.Chinese Acad Sci, Brain Cognit & Brain Dis Inst, Shenzhen Inst Adv Technol, Interdisciplinary Ctr Brain Informat, Shenzhen 518055, Guangdong, Peoples R China
6.Chinese Acad Sci, Shenzhen Inst Adv Technol, Fac Life & Hlth Sci, Shenzhen 518055, Guangdong, Peoples R China
7.Shenzhen Fundamental Res Inst, Shenzhen Hong Kong Inst Brain Sci, Shenzhen 518055, Guangdong, Peoples R China
8.Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen 518055, Guangdong, Peoples R China
9.Sun Yat Sen Univ, Sch Life Sci, State Key Lab Biocontrol, Guangzhou 510275, Peoples R China
10.Southern Univ Sci & Technol, Cryo EM Facil Ctr, Shenzhen 518055, Guangdong, Peoples R China
11.Shenzhen Univ, Guangdong Prov Res Ctr Artificial Intelligence & D, Shenzhen Intelligent Orthopaed & Biomed Innovat Pl, Dept Orthoped,Shenzhen Peoples Hosp 2,Affiliated H, Shenzhen 518000, Guangdong, Peoples R China
12.Southern Univ Sci & Technol, Guangdong Prov Key Lab Adv Biomat, Shenzhen 518055, Guangdong, Peoples R China

Zhu, Kong-Fu,Yuan, Chuang,Du, Yong-Ming,et al. Applications and prospects of cryo-EM in drug discovery[J]. Military Medical Research,2023,10(1).

Zhu, Kong-Fu.,Yuan, Chuang.,Du, Yong-Ming.,Sun, Kai-Lei.,Zhang, Xiao-Kang.,...&Zhang, Hua-Wei.(2023).Applications and prospects of cryo-EM in drug discovery.Military Medical Research,10(1).

Zhu, Kong-Fu,et al."Applications and prospects of cryo-EM in drug discovery".Military Medical Research 10.1(2023).