Genomics and Applied Biology 2024, Vol.15, No.1, 27-38 http://bioscipublisher.com/index.php/gab 32 demonstrating the powerful ability of cryo EM in capturing different protein conformations and providing atomic level resolution structures. In addition, cryo electron microscopy can not only capture the static structure of proteins, but also reveal their dynamic transitions between different states, providing valuable information for understanding protein responses to biochemical signals or interactions with other molecules. By combining the structural data of cryo electron microscopy with data from other biochemical and biophysical technologies, scientists can comprehensively understand the function of proteins from multiple perspectives, thereby revealing their roles in complex biological processes. 3 Application of Cryo Electron Microscopy Technology in Protein Structure Analysis 3.1 High resolution protein structure analysis The application of cryo electron microscopy (Cryo EM) in the field of protein structure analysis marks a significant advancement in biochemical and molecular biology research, especially in achieving high-resolution protein structure analysis. This technology enables scientists to reveal the three-dimensional structure of proteins with near atomic level clarity, thereby gaining a deeper understanding of their biological functions. Freezing electron microscopy technology is also particularly suitable for analyzing the heterogeneity and dynamics of proteins, capturing the instantaneous state of protein transitions between various conformations. This is crucial for understanding how macromolecular machines and complexes perform their functions through precise assembly and dynamic changes in their components. In the study of ribosomes, membrane protein complexes, and viral particles, cryoelectron microscopy has become an irreplaceable tool. For example, Yi (2018) proposed a method that combines microfluidic single-cell extraction with electron microscopy single particle analysis to characterize protein complexes from individual Caenorhabditis elegans embryos, revealing the structure of ribosomes directly from single embryo extracts. In addition, the contribution of cryo electron microscopy to drug discovery and design cannot be underestimated. By providing high-resolution structural images of target proteins, it provides drug designers with the basis for designing highly specific drugs that can more effectively bind to target proteins, improve efficacy, and reduce side effects. In the development process of antiviral drugs and cancer therapeutic agents, cryo electron microscopy has shown its enormous potential. Renaud et al. (2018) found that historically, the application of cryo EM in drug discovery has been extremely limited by the minimum size of the structures it can be used to study and the resolution of the images. However, the development of direct electronic detectors and the latest advances in more effective computational image analysis techniques are overturning the practicality of cryo EM, leading to the explosion of high-resolution structures assembled with a large number of large macromolecules. These advances enhance the hope that single particle cryo EM may soon become an important tool in drug discovery, especially if they can make it possible to determine the structure of "difficult to handle" targets that currently cannot be analyzed by X-ray crystallography. By analyzing the multi protein interactions that make up large complexes, cryo electron microscopy revealed the mechanisms of complex biological processes such as intracellular signal transduction networks, protein synthesis, decomposition, and pathogen invasion. For example, Chen et al. (2020) discussed the method of using generative adversarial networks (a form of artificial intelligence) to denoise individual particles, which effectively restores the global structural information of synthetic and real cryo EM data, providing assistance in evaluating individual particles from noisy original images. With the continuous advancement of detector technology, image processing software, and sample preparation methods, the resolution and application range of cryo electron microscopy continue to expand, making it the preferred technology for biomolecular structure analysis. 3.2 Structural analysis of complex protein complexes Complex protein complexes, such as those involved in cellular signaling, gene expression regulation, and immune response, are often difficult to cope with traditional structural analysis methods due to their high complexity and
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