GAB_2024v15n1

Genomics and Applied Biology 2024, Vol.15, No.1, 27-38 http://bioscipublisher.com/index.php/gab 34 valuable information for a deeper understanding of the functions of these biomolecules. 4 Latest Developments 4.1 Application of New Detectors The application of new detectors in cryo electron microscopy (Cryo EM) technology marks a significant improvement in protein structure analysis ability, triggering a technological revolution in this field. These advanced direct electron detectors greatly enhance the resolution and quality of images, providing scientists with unprecedented detailed perspectives on observing the structure and function of biological macromolecules. The high frame rate imaging capability of the new detector has opened up a new way to study the dynamic changes of proteins, enabling scientists to capture a large number of images in a very short time, thereby observing and analyzing the structural changes of proteins in different functional states. This is particularly important for understanding dynamic proteins that rely on rapid conformational changes to perform their biological functions, providing a powerful analytical tool. With the surge in data volume, new detectors have also brought challenges in data processing and analysis. To address this challenge, it is possible to develop more efficient image processing algorithms and software that can quickly extract meaningful structural information from large datasets, accelerate the process of structural analysis, and improve its accuracy. Cheng et al. (2015) outlined the different steps and considerations in determining the structure of single particle cryo EM, with particular emphasis on the latest advances in detector technology and software algorithms, which now allow for recording unprecedented quality images and determining the structure at near atomic resolution. Faruqi and McMullan (2018) reviewed the electronic detectors used in electron microscopy imaging, emphasizing the advantages of direct imaging detectors in terms of improved resolution, fast readout speed, and sufficient resistance to radiation hardness. Spilman (2020) discussed how the development of direct detection cameras has led to unprecedented improvements in the quality of recorded images. These large format (>4 million pixels) cameras can provide continuous image streams and have near ideal detection quantum efficiency (DQE), which has led to the important role of bioelectronic cryo EM in the "resolution revolution". The introduction of new detectors not only improves the resolution and processing efficiency of images, but also greatly expands the application range of cryo electron microscopy technology, enabling scientists to study small molecule proteins and complex biomolecular complexes that were previously difficult to decipher. These advances have had profound impacts on drug discovery, virological research, and many other aspects of the biomedical field. 4.2 Development of automatic data collection and analysis In the field of cryo electron microscopy (Cryo EM) technology, the development of automated data collection and analysis has become the core driving force for advancing protein structure analysis. This progress not only significantly improves the efficiency of experiments, but also improves data quality, making it possible to process large datasets and accelerating the entire process from data collection to structural analysis. Through automated systems for data collection, scientists can achieve rapid identification, localization, autofocus, and calibration of potential areas on the sample grid while reducing human intervention, thus efficiently collecting image data under preset conditions. This automated process not only improves the consistency and repeatability of image acquisition, but also greatly accelerates the collection speed of a large amount of high-quality data. Danev et al. (2019) emphasized the latest technological and methodological developments in cryo EM, including single particle analysis (SPA) and cryo electron chromatography (cryo ET), which have made automated data

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