Genomics and Applied Biology 2024, Vol.15, No.1, 27-38 http://bioscipublisher.com/index.php/gab 28 This study aims to explore the latest advances in protein structure analysis using cryo electron microscopy technology, and to reveal the potential and value of cryo electron microscopy technology in the field of protein structure research. This study reviews the development history of cryo electron microscopy technology, outlines its advantages and applications in protein structure analysis, and looks forward to the future development trends of cryo electron microscopy technology in protein structure analysis, in order to provide useful references and insights for researchers in this field. Through this study, it is expected to promote the further development of cryoelectron microscopy technology and provide more efficient and accurate tools and methods for protein structure research in the fields of biology and medicine. 1 The Development History of Cryoelectron Microscopy Technology 1.1 Limitations of early cryoelectron microscopy techniques The development history of cryoelectron microscopy technology has a long history, going from early exploration and experimentation to today's maturity and widespread application. In the early stages, cryoelectron microscopy technology faced many limitations and challenges. Chlanda and Locker (2017) discussed how the development of electron microscopy (EM) technology for biological samples from the 1940s to the 1950s changed people's understanding of eukaryotic cell architecture, and how in the following decades, despite the emergence of significant new methods, EM technology seemed to have entered a dormant phase. The discovery of rapidly frozen samples gave birth to the world of cryo EM, and in the past 15-20 years, cryo EM has aroused great interest due to significant technological advancements. In the 1960s, cryo electron microscopy imaging technology began to develop as a branch of scanning electron microscopy imaging technology. However, before the 1970s, the application of cryoelectron microscopy technology was mainly concentrated in the fields of polymer chemistry and biochemistry, and its imaging effects were not ideal. This was mainly due to technical limitations at the time, such as low instrument resolution and severe radiation damage, which made it difficult to obtain high-quality cryo electron microscopy images. In the 1970s, researchers began to explore methods to improve the resolution of cryo electron microscopy samples. The resolution of the sample has been improved to a certain extent through gas enhanced freezing technology, but there are still many limitations. At this time, cryo electron microscopy technology still faces difficulties in sample preparation and unstable imaging effects, which greatly limits its application in protein structure analysis and other fields. In the 1980s, with the rapid development of computer technology, cryoelectron microscopy imaging technology was significantly improved. Taylor and Glaeser (2008) found that advances in computer technology have made image processing and analysis more precise and efficient, thereby improving the resolution and reliability of cryoelectron microscopy images. At the same time, researchers are constantly optimizing the freezing sample preparation technology to reduce the formation of ice crystals, allowing the samples to maintain better structural integrity in the frozen state. Despite significant progress made in the 1980s, cryoelectron microscopy technology still faces some challenges. For example, imaging of large biomolecular complexes remains challenging, and the potential radiation damage during the imaging process has not been fully resolved. 1.2 Technological breakthroughs and improvements In the development process of cryo electron microscopy technology, technological breakthroughs and improvements have played a crucial role, driving its application in protein structure analysis and other fields to continuously advance. Tsuchiya (2019) found that early cryoelectron microscopy techniques faced the problem of ice crystal formation during the freezing process of samples, which greatly affected the quality of imaging. Researchers developed rapid freezing and vitrification techniques, effectively reducing the formation of ice crystals and improving the resolution of cryoelectron microscopy imaging.
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