Bioscience Method 2024, Vol.15, No.2, 50-57 http://bioscipublisher.com/index.php/bm 55 3.2 How cryo-EM accelerates the discovery and development of new drugs Cryo-electron microscopy (cryo-EM) significantly accelerates the process of new drug discovery and development through its unique capabilities. In the early stages of drug discovery, cryo-EM provides high-resolution structural information of biological macromolecular targets, enabling research teams to more precisely understand the three-dimensional structure and characteristics of these targets. This precise structural information is crucial for drug screening and design, as it helps identify drug candidates that can effectively bind to the target. Cryo-EM reveals the intricate details of the interactions between drugs and biological macromolecules. By observing how drug molecules bind to targets and how this binding affects the target’s function and activity, a deeper understanding of the drug’s mechanism of action can be achieved. This understanding not only aids in predicting the drug’s efficacy and side effects but also guides further drug optimization and improvement efforts (Sara et al., 2021). Furthermore, cryo-EM accelerates the iterative process of drug development. In traditional drug development workflows, screening and optimizing drug candidates typically require multiple rounds of experiments and testing. However, using the high-resolution structural and interaction information provided by cryo-EM, potential drug candidates can be identified early on, and structural optimization can be rapidly conducted. This significantly reduces the time and cost of drug development, enhancing research and development efficiency. 3.3 Future trends of cryo-electron microscopy in drug discovery and design The future trends of cryo-electron microscopy in drug discovery and design suggest that it will continue to play a significant role and will be combined with other advanced technologies to drive greater breakthroughs in the field of drug research and development. With technological advancements, the resolution and imaging speed of cryo-electron microscopy will further improve, allowing for more detailed observation of the interactions between drugs and biomolecules. This will contribute to a deeper understanding of the mechanisms of drugs, providing more precise and comprehensive information for drug discovery and design. The integration of cryo-electron microscopy with other technologies will foster innovation in the drug development process. Twarock and Stockley (2019) found that combining it with artificial intelligence and machine learning algorithms can facilitate rapid screening and optimization of a large number of drug candidates. By integrating with multi-omics data such as genomics, proteomics, and metabolomics, cryo-electron microscopy will be able to provide more comprehensive and holistic information about the structure and function of biomolecules, offering a broader perspective for drug discovery and design. Additionally, cryo-electron microscopy will also play an important role in other aspects of new drug development. For example, in the optimization of drug crystal forms, cryo-electron microscopy can reveal the structure and stability of different crystal forms of drug molecules, providing guidance for the development of drug formulations. In studies of drug interactions with cell membranes, cryo-electron microscopy will be able to reveal how drugs penetrate cell membranes and interact with them, providing crucial insights for the development of drugs with better bioavailability. 4 Summary and Outlook Cryo-electron microscopy has played a crucial role in elucidating the mechanisms of drug action. It not only provides high-resolution images of the interactions between drugs and biomolecules, but also reveals in detail the dynamic processes of these interactions. Through cryo-electron microscopy, it is possible to precisely identify the binding sites of drug molecules on biomolecules, and understand how drugs exert their therapeutic effects by interfering with or regulating the functions of biomolecules (Zhu et al., 2021). This deep understanding not only enhances our knowledge of drug mechanisms but also provides important theoretical support and experimental evidence for drug research and optimization.
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