Bioscience Method 2024, Vol.15, No.2, 50-57 http://bioscipublisher.com/index.php/bm 50 Review and Progress Open Access Structural Analysis of Drugs by Cryo-electron Microscopy Reveals Their Mechanisms of Action Jiayao Zhou Institute of Life Science, Jiyang College of Zhejiang A&F University, Zhuji, 311800, China Corresponding email: 2013478397@qq.com Bioscience Method, 2024, Vol.15, No.2 doi: 10.5376/bm.2024.15.0006 Received: 02 Jan., 2024 Accepted: 13 Feb., 2024 Published: 01 Mar., 2024 Copyright © 2024 Zhou, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Zhou J.Y., 2024, Structural analysis of drugs by cryo-electron microscopy reveals their mechanisms of action, Bioscience Method, 15(2): 50-57 (doi: 10.5376/bm.2024.15.0006) Abstract Cryo-electron microscopy is a crucial tool for studying the mechanisms of drug action, as it provides high-resolution structural analysis of biological macromolecules, revealing the interactions between drugs and these macromolecules. This study delves into the importance of drug action mechanisms and the challenges they pose. It begins by introducing the principles, workflow, and widespread applications of cryo-electron microscopy in biological macromolecule structure analysis, particularly its unique advantages in drug mechanism studies. Through several successful cases, the study illustrates the practical applications of cryo-electron microscopy in drug mechanism analysis, explores its use in drug screening and optimization, and how it can accelerate the discovery and development of new drugs. The paper concludes by summarizing the significant role of cryo-electron microscopy in drug mechanism analysis and looking ahead to its future potential and applications in drug research and development. This research aims to provide new perspectives and methods for studying drug action mechanisms through cryo-electron microscopy, contributing to the advancement of drug discovery and development. Keywords Cryo-electron microscopy; Drug mechanism of action; Biological macromolecule structure; Drug discovery; Interaction mechanism The mechanism of drug action is a core issue in drug development, determining how drugs interact with biological systems to produce therapeutic effects and possible side effects. Drug interactions in the body usually involve multiple biomolecules, such as proteins and nucleic acids, which are structurally complex and functionally diverse, making these interactions highly intricate. Traditional research methods, such as biochemical analysis and genetic techniques, although informative, often fail to fully reveal the detailed mechanisms of drug interactions with biomolecules (Radostin et al., 2019). In this context, cryo-electron microscopy (cryo-EM) has emerged as a prominent technique due to its unique advantages. Cryo-EM can capture the structures of biomolecules under near-physiological conditions and provide near-atomic resolution images, allowing researchers to directly observe the details of drug interactions with biomolecules. Moreover, cryo-EM can capture the dynamic changes of biomolecules, offering insights into the dynamic mechanisms of drug action (Cheng, 2018; Nannenga and Gonen, 2018). This review aims to explore the application of cryo-EM in studying the mechanisms of drug action, revealing its potential and advantages in elucidating drug interactions with biomolecules. The manuscript introduces the basic principles and workflow of cryo-EM and discusses its widespread use in structural analysis of biomolecules. Through case studies, it demonstrates how cryo-EM provides robust support in deciphering drug action mechanisms, including drug binding modes and drug-induced conformational changes. The discussion extends to the application of cryo-EM in drug screening and optimization, and its role in advancing new drug discovery and development. This review seeks to provide a new perspective and approach to the research on drug action mechanisms, aiming to advance the field of drug development. It also hopes to draw more researchers' attention to and interest in cryo-EM, encouraging the exploration of its broader applications in drug research. With ongoing technological advancements, cryo-EM is expected to play an increasingly significant role in studying drug action mechanisms, contributing greatly to human health endeavors.
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